Syringe with pecvd lubrication

ABSTRACT

A syringe or other vessel having a substrate surface coated by PECVD is provided. The PECVD coating is made by generating plasma from a gaseous reactant comprising an organosilicon precursor and optionally O2. The lubricity, hydrophobicity and/or barrier properties of the coating are set by setting the ratio of the O2 to the organosilicon precursor in the gaseous reactant, and/or by setting the electric power used for generating the plasma. In particular, a lubricity coating made by said method is provided. Vessels coated by said method and the use of such vessels protecting a compound or composition contained or received in said coated vessel against mechanical and/or chemical effects of the surface of the uncoated vessel material are also provided.

This application is a continuation of U.S. Ser. No. 13/697,048, filed onMay 11, 2011, which is a 371 of international of PCT/US2011/036097 filedon May 11, 2011, which is a continuation-in-part of U.S. Ser. No.12/779,007, filed on May 12, 2010, and issued as U.S. Pat. No. 7,985,188on Jul. 26, 2011. All of these applications are incorporated here byreference in their entireties.

U.S. Ser. No. 13/697,048, filed on May 11, 2011, is also acontinuation-in-part of PCT/US2010/034586, filed May 12, 2010, andclaims the benefit of the following: U.S. Provisional Application No.61,359,434, filed Jun. 29, 2010, U.S. Provisional Application No.61/413,334 filed Nov. 12, 2010, U.S. Provisional Application No.61/452,256, filed Mar. 14, 2011. All of these applications areincorporated here by reference in their entireties.

U.S. Provisional Ser. Nos. 61/177,984 filed May 13, 2009; 61/222,727,filed Jul. 2, 2009; 61/213,904, filed Jul. 24, 2009; 61/234,505, filedAug. 17, 2009; 61/261,321, filed Nov. 14, 2009; 61/263,289, filed Nov.20, 2009; 61/285,813, filed Dec. 11, 2009; 61/298,159, filed Jan. 25,2010; 61/299,888, filed Jan. 29, 2010; 61/318,197, filed Mar. 26, 2010;61/333,625, filed May 11, 2010; and 61/413,334, filed Nov. 12, 2010; andU.S. Ser. No. 12/779,007, filed May 12, 2010, are all incorporated hereby reference in their entirety.

Also incorporated by reference in their entirety are the followingEuropean patent applications: EP10162755.2 filed May 12, 2010;EP10162760.2 filed May 12, 2010; EP10162756.0 filed May 12, 2010;EP10162758.6 filed May 12, 2010; EP10162761.0 filed May 12, 2010; andEP10162757.8 filed May 12, 2010. These European patent applicationsdescribe apparatus, vessels, precursors, coatings and methods (inparticular coating methods and test methods for examining the coatings)which can generally be used in performing the present invention, unlessstated otherwise herein. They also describe SiO_(x) barrier coatings towhich reference is made herein.

FIELD OF THE INVENTION

The present invention relates to the technical field of fabrication ofcoated vessels for storing biologically active compounds or blood. Forexample, the invention relates to a vessel processing system for coatingof a vessel, vessel processing system for coating and inspection of avessel, to a plasma enhanced chemical vapour deposition apparatus forcoating an interior surface of a vessel, to a method for coating aninterior surface of a vessel, to a method for coating and inspection ofa vessel, to a method of processing a vessel, to the use of a vesselprocessing system, to a computer-readable medium and to a programelement.

A method for coating a substrate surface by PECVD is provided, themethod comprising generating a plasma from a gaseous reactant comprisingan organosilicon precursor and optionally O₂. A carrier gas may also bepresent. The lubricity, hydrophobicity and/or barrier properties of thecoating are set by setting the ratio of the O₂ to the organosiliconprecursor and to the carrier gas in the gaseous reactant, and/or bysetting the electric power used for generating the plasma. Inparticular, a lubricity coating made by said method is provided. Vesselscoated by said method and the use of such vessels protecting a compoundor composition contained or received in said coated vessel againstmechanical and/or chemical effects of the surface of the uncoated vesselmaterial are also provided. Further provided are surfaces coated withthe lubricity coating, and methods for production of said lubricitycoating.

The present disclosure also relates to improved methods for processingvessels, for example multiple identical vessels used for venipunctureand other medical sample collection, pharmaceutical preparation storageand delivery, and other purposes. Such vessels are used in large numbersfor these purposes, and must be relatively economical to manufacture andyet highly reliable in storage and use.

BACKGROUND OF THE INVENTION

An important consideration when regarding syringes is to ensure that theplunger can move at a constant speed and with a constant force when itis pressed into the barrel. For this purpose, a lubricity layer, eitheron one or on both of the barrel and the plunger, is desirable. A similarconsideration applies to vessels which have to be closed by a stopper,and to the stopper itself, and more generally to any surface which hasto provide a certain lubricity.

There are additional considerations to be taken into account whenmanufacturing a prefilled syringe. Prefilled syringes are commonlyprepared and sold so the syringe does not need to be filled before use.The syringe can be prefilled with saline solution, a dye for injection,or a pharmaceutically active preparation, for some examples.

Commonly, the prefilled syringe is capped at the distal end, as with acap, and is closed at the proximal end by its drawn plunger. Theprefilled syringe can be wrapped in a sterile package before use. To usethe prefilled syringe, the packaging and cap are removed, optionally ahypodermic needle or another delivery conduit is attached to the distalend of the barrel, the delivery conduit or syringe is moved to a useposition (such as by inserting the hypodermic needle into a patient'sblood vessel or into apparatus to be rinsed with the contents of thesyringe), and the plunger is advanced in the barrel to inject thecontents of the barrel.

One important consideration in manufacturing pre-filled syringes is thatthe contents of the syringe desirably will have a substantial shelflife, during which it is important to isolate the material filling thesyringe from the barrel wall containing it, to avoid leaching materialfrom the barrel into the prefilled contents or vice versa.

Since many of these vessels are inexpensive and used in largequantities, for certain applications it will be useful to reliablyobtain the necessary shelf life without increasing the manufacturingcost to a prohibitive level. For decades, most parenteral therapeuticshave been delivered to end users in Type I medical grade borosilicateglass containers such as vials or pre-filled syringes. The relativelystrong, impermeable and inert surface of borosilicate glass hasperformed adequately for most drug products. However, the recent adventof costly, complex and sensitive biologics as well as such advanceddelivery systems as auto injectors has exposed glass' physical andchemical shortcomings including possible contamination from metals andbreakage, among other problems. Moreover, glass contains severalcomponents which can leach out during storage and cause damage to thestored material. In more detail, borosilicate vessels exhibit a numberof drawbacks:

Glass is manufactured from sand containing a heterogeneous mixture ofmany elements (silicon, oxygen, boron, aluminum, sodium, calcium) withtrace levels of other alkali and earth metals. Type I borosilicate glassconsists of approximately 76% SiO₂, 10.5% B₂O₃, 5% Al₂O₃, 7% Na_(2O) and1.5% CaO and often contains trace metals such as iron, magnesium, zinc,copper and others. The heterogeneous nature of borosilicate glasscreates a non-uniform surface chemistry at the molecular level. Glassforming processes used to create glass containers expose some portionsof the containers to temperatures as great as 1200° C. Under such hightemperatures alkali ions migrate to the local surface and form oxides.The presence of ions extracted from borosilicate glass devices may beinvolved in degradation, aggregation and denaturation of some biologics.Many proteins and other biologics must be lyophilized (freeze dried),because they are not sufficiently stable in solution in glass vials orsyringes.

In glass syringes, silicon oil is typically used as a lubricant to allowthe plunger to slide in the barrel. Silicon oil has been implicated inthe precipitation of protein solutions such as insulin and some otherbiologics. Additionally, the silicon oil coating is often non-uniform,resulting in syringe failures in the market.

Glass vessels are prone to breakage or degradation during manufacture,filling operations, shipping and use, which means that glassparticulates may enter the drug. The presence of glass particles has ledto many FDA Warning Letters and to product recalls.

Glass-forming processes do not yield the tight dimensional tolerancesrequired for some of the newer auto-injectors and delivery systems.

As a result, some companies have turned to plastic vessels, whichprovide greater dimensional tolerance and less breakage than glass butlack its impermeability.

Although plastic is superior to glass with respect to breakage,dimensional tolerances and surface uniformity, plastic's use for primarypharmaceutical packaging remains limited due to the followingshortcomings:

Surface characteristics: Plastics suitable for pre-syringes and vialsgenerally exhibit hydrophobic surfaces, which often reduce the stabilityof the biologic drug contained in the device.

Gas (oxygen) permeability: Plastic allows small molecule gases topermeate into (or out of) the device. Plastics' permeability to gases issignificantly greater than that of glass and, in many cases (as withoxygen-sensitive drugs such as epinephrine), plastics are unacceptablefor that reason.

Water vapor transmission: Plastics allow water vapors to pass throughdevices to a greater degree than glass. This can be detrimental to theshelf life of a solid (lyophilized) drug. Alternatively, a liquidproduct may lose water in an arid environment.

Leachables and extractables: Plastic vessels contain organic compoundsthat can leach out or be extracted into the drug product. Thesecompounds can contaminate the drug and/or negatively impact the drug'sstability.

Clearly, while plastic and glass vessels each offer certain advantagesin pharmaceutical primary packaging, neither is optimal for all drugs,biologics or other therapeutics. Thus, there is a desire for plasticvessels, in particular plastic syringes, with gas and solute barrierproperties which approach the properties of glass. Moreover, there is aneed for plastic syringes with sufficient lubricity properties and alubricity coating which is compatible with the syringe contents.

A non-exhaustive list of patents of possible relevance includes U.S.Pat. Nos. 6,068,884 and 4,844,986 and U.S. Published Applications20060046006 and 20040267194.

SUMMARY OF THE INVENTION

The present invention pertains to plastic vessels, in particular vialsand syringes, coated with thin, PECVD coatings made from organosiliconprecursors. These novel devices offer the superior barrier properties ofglass and the dimensional tolerances and breakage resistance ofplastics, yet eliminate the drawbacks of both materials. With designedmodifications to the PECVD process, the surface chemistry of the coatingcan be predictably varied. In particular, a plasma coating (SiOxCyHz) isprovided which improves lubricity (“lubricity coating”), thuseliminating the need for traditional silicon oil lubricants e.g. insyringes. Further embodiments of the invention are methods to influencethe hydrophobicity/hydrophilicity of said coatings and the resultingcoated devices.

A particular embodiment of present invention is a plastic (inparticular, COC) syringe coated with a Si_(w)O_(x)C_(y)H_(z) coatingproviding lubricity to the syringe interior, thus eliminatingtheextractables from traditional silicon oil. The lubricity coating can beon the syringe barrel, the plunger (or one of its parts, e.g. the sidewalls of the piston), or both. Such syringe can also in addition have aSiO_(x) barrier coating made by PECVD according to the presentinvention. A very particular embodiment is a syringe having a cyclicolefin copolymer (COC) barrel, a SiO_(x) barrier layer on the inner wallof said barrel, and a lubricity layer on said barrier layer. A SiOxbarrier coating typically is 20 to 30 nm thick.

The coatings described herein are glass-like, but do not contain otherelements such as boron, sodium, calcium, aluminum and impurities foundin glass.

The coatings have a surface free of deleterious elements and impuritiesfound in Type I medical grade borosilicate glass. The coating isdeposited on a plastic substrate from plasma, which utilizesorganosilicons, creating a uniform layer.

The invention further pertains to a vessel processing system for coatingof a vessel, the system comprising a processing station arrangementconfigured for performing the above and/or below mentioned method steps.Examples of such processing stations 5501-5504 are depicted in FIG.12-14.

The invention further pertains to a computer-readable medium, in which acomputer program for coating of a vessel is stored which, when beingexecuted by a processor of a vessel processing system, is adapted toinstruct the processor to control the vessel processing system such thatit carries out the above and/or below mentioned method steps.

The invention further pertains to a program element or computer programfor coating of a vessel, which, when being executed by a processor of avessel processing system, is adapted to instruct the processor tocontrol the vessel processing system such that it carries out the aboveand/or below mentioned method steps.

The processor may thus be equipped to carry out exemplary embodiments ofthe methods of the present invention. The computer program may bewritten in any suitable programming language, for example, C++ and maybe stored on the computer-readable medium, such as a CD-ROM. Also, thecomputer program may be available from a network, such as theWorldWideWeb, from which it may be downloaded into image processingunits or processors, or any suitable computers.

In the following, coating methods according to the invention and coateddevices according to the invention which are made by these methods aredescribed. The methods can be carried out on the equipment (vesselprocessing system and vessel holder) which is also described below.

PECVD Coating Method

The present invention pertains to a method of preparing a coating byplasma enhanced chemical vapor deposition treatment (PECVD), and forexample a method of coating the interior surface of a vessel.

A surface, for example an interior vessel surface, is provided, as is areaction mixture comprising an organosilicon compound gas, optionally anoxidizing gas, optionally a hydrocarbon gas, and optionally a carriergas. For preparing a lubricity coating, a mixture of an organosiliconprecursor (e.g. OMCTS), Oxygen and Argon is preferred.

The surface is contacted with the reaction mixture. Plasma is formed inthe reaction mixture. The coating is deposited on at least a portion ofthe surface, e.g. a portion of the vessel interior wall.

The method is carried out as follows.

A precursor is provided. Preferably, said precursor is an organosiliconcompound (in the following also designated as “organosiliconprecursor”), more preferably an organosilicon compound selected from thegroup consisting of a linear siloxane, a monocyclic siloxane, apolycyclic siloxane, a polysilsesquioxane, an alkyl trimethoxysilane, anaza analogue of any of these precursors (i.e. a linear siloxazane, amonocyclic siloxazane, a polycyclic siloxazane, a polysilsesquioxazane),and a combination of any two or more of these precursors. The precursoris applied to a substrate under conditions effective to form a coatingby PECVD. The precursor is thus polymerized, crosslinked, partially orfully oxidized, or any combination of these.

In one aspect of the invention, the coating is a lubricity coating, i.e.it forms a surface having a lower frictional resistance than theuncoated substrate.

In another aspect of the invention, the coating is a passivatingcoating, for example a hydrophobic coating resulting, e.g., in a lowerprecipitation of components of a composition in contact with the coatedsurface. Such hydrophobic coating is characterized by a lower wettingtension than its uncoated counterpart.

A lubricity coating of the present invention may also be a passivatingcoating and vice versa.

In a further aspect of the invention, the coating is a barrier coating,for example an SiO_(x) coating. Typically, the barrier is against a gasor liquid, preferably against water vapor, oxygen and/or air. Thebarrier may also be used for establishing and/or maintaining a vacuuminside a vessel coated with the barrier coating, e.g. inside a bloodcollection tube.

The method of the invention may comprise the application of one or morecoatings made by PECVD from the same or different organosiliconprecursors under the same or different reaction conditions. E.g. ssyringe may first be coated with an SiO_(x) barrier coating using HMDSOas organosilicon precursor, and subsequently with a lubricity coatingusing OMCTS as organosilicon precursor.

Lubricity Coating

In its main aspect, the present invention provides a lubricity coating.

This coating is advantageously made by the PECVD method and using theprecursors as described above. A preferred precursor for the lubricatingcoating is a monocyclic siloxane, for exampleoctamethylcyclotetrasiloxane (OMCTS).

For example, the present invention provides a method for setting thelubricity properties of a coating on a substrate surface, the methodcomprising the steps:

-   -   (a) providing a gas comprising an organosilicon precursor and        optionally O₂ and optionally a noble gas (e.g. Argon) in the        vicinity of the substrate surface; and    -   (b) generating a plasma from the gas, thus forming a coating on        the substrate surface by plasma enhanced chemical vapor        deposition (PECVD), wherein the lubricity characteristics of the        coating are set by setting the ratio of the O₂ to the        organosilicon precursor in the gaseous reactant, and/or by        setting the electric power used for generating the plasma,        and/or by setting the ratio of the noble gas to the        organosilicon precursor.

The resulting coated surface has a lower frictional resistance than theuntreated substrate. For example, when the coated surface is the insideof a syringe barrel and/or a syringe plunger, the lubricity coating iseffective to provide a breakout force or plunger sliding force, or both,that is less than the corresponding force required in the absence of thelubricating coating.

The article coated with the lubricity coating may be a vessel having thelubricating coating on a wall, preferably on the interior wall, e.g. asyringe barrel, or a vessel part or vessel cap having said coating onthe vessel contacting surface, e.g. a syringe plunger or a vessel cap.

The lubricity coating typically has a formula Si_(w)O_(x)C_(y)H_(z). Itgenerally has an atomic ratio Si_(w)O_(x)C_(y) wherein w is 1, x is fromabout 0.5 to about 2.4, y is from about 0.6 to about 3, preferably w is1, x is from about 0.5 to 1.5, and y is from 0.9 to 2.o, more preferablyw is 1, x is from 0.7 to 1.2 and y is from 0.9 to 2.0. The atomic ratiocan be determined by XPS (X-ray photoelectron spectroscopy). Taking intoaccount the H atoms, the lubricity coating may thus in one aspect havethe formula Si_(w)O_(x)C_(y)H_(z), for example where w is 1, x is fromabout 0.5 to about 2.4, y is from about 0.6 to about 3, and z is fromabout 2 to about 9. Typically, the atomic ratios are Si 100: O 80-110: C100-150 in a particular lubricity coating of present invention.Specifically, the atomic ratio may be Si 100: O 92-107: C 116-133, andsuch lubricity coating would hence contain 36% to 41% carbon normalizedto 100% carbon plus oxygen plus silicon.

Passivating, for Example Hydrophobic Coating

The passivating coating according to the present invention is forexample a hydrophobic coating.

A preferred precursor for the passivating, for example the hydrophobiccoating is a linear siloxane, for example hexamethyldisiloxane (HMDSO).

A passivating coating according to the present invention prevents orreduces mechanical and/or chemical effects of the uncoated surface on acompound or composition contained in the vessel. For example,precipitation and/or clotting or platelet activation of a compound orcomponent of a composition in contact with the surface are prevented orreduced, e.g. blood clotting or platelet activation or precipitation ofinsulin, or wetting of the uncoated surface by an aqueous fluid isprevented.

A particular aspect of the invention is a surface having a hydrophobiccoating with the formula Si_(w)O_(x)C_(y)H_(z). It generally has anatomic ratio Si_(w)O_(x)C_(y) wherein w is 1, x is from about 0.5 toabout 2.4, y is from about 0.6 to about 3, preferably w is 1, x is fromabout 0.5 to 1.5, and y is from 0.9 to 2.0, more preferably w is 1, x isfrom 0.7 to 1.2 and y is from 0.9 to 2.0. The atomic ratio can bedetermined by XPS (X-ray photoelectron spectroscopy). Taking intoaccount the H atoms, the hydrophobic coating may thus in one aspect havethe formula Si_(w)O_(x)C_(y)H_(z), for example where w is 1, x is fromabout 0.5 to about 2.4, y is from about 0.6 to about 3, and z is fromabout 2 to about 9. Typically, the atomic ratios are Si 100: O 80-110: C100-150 in a particular hydrophobic coating of present invention.Specifically, the atomic ratio may be Si 100: O 92-107: C 116-133, andsuch coating would hence contain 36% to 41% carbon normalized to 100%carbon plus oxygen plus silicon.

The article coated with the passivating coating may be a vessel havingthe coating on a wall, preferably on the interior wall, e.g. a tube, ora vessel part or vessel cap having said coating on the vessel contactingsurface, e.g. a vessel cap.

Coating of a Vessel

When a vessel is coated by the above coating method using PECVD, thecoating method comprises several steps. A vessel is provided having anopen end, a closed end, and an interior surface. At least one gaseousreactant is introduced within the vessel. Plasma is formed within thevessel under conditions effective to form a reaction product of thereactant, i.e. a coating, on the interior surface of the vessel.

Preferably, the method is performed by seating the open end of thevessel on a vessel holder as described herein, establishing a sealedcommunication between the vessel holder and the interior of the vessel.In this preferred aspect, the gaseous reactant is introduced into thevessel through the vessel holder. In a particularly preferred aspect ofthe invention, a plasma enhanced chemical vapor deposition (PECVD)apparatus comprising a vessel holder, an inner electrode, an outerelectrode, and a power supply is used for the coating method accordingto the present invention.

The vessel holder has a port to receive a vessel in a seated positionfor processing. The inner electrode is positioned to be received withina vessel seated on a vessel holder. The outer electrode has an interiorportion positioned to receive a vessel seated on the vessel holder. Thepower supply feeds alternating current to the inner and/or outerelectrodes to form a plasma within the vessel seated on the vesselholder. Typically, the power supply feeds alternating current to theouter electrode while the inner electrode is grounded. In thisembodiment, the vessel defines the plasma reaction chamber.

In a particular aspect of the invention, the PECVD apparatus asdescribed in the preceding paragraphs comprises a gas drain, notnecessarily including a source of vacuum, to transfer gas to or from theinterior of a vessel seated on the port to define a closed chamber.

In a further particular aspect of the invention, the PECVD apparatusincludes a vessel holder, a first gripper, a seat on the vessel holder,a reactant supply, a plasma generator, and a vessel release.

The vessel holder is configured for seating to the open end of a vessel.The first gripper is configured for selectively holding and releasingthe closed end of a vessel and, while gripping the closed end of thevessel, transporting the vessel to the vicinity of the vessel holder.The vessel holder has a seat configured for establishing sealedcommunication between the vessel holder and the interior space of thefirst vessel.

The reactant supply is operatively connected for introducing at leastone gaseous reactant within the first vessel through the vessel holder.The plasma generator is configured for forming plasma within the firstvessel under conditions effective to form a reaction product of thereactant on the interior surface of the first vessel.

The vessel release is provided for unseating the first vessel from thevessel holder. A gripper which is the first gripper or another gripperis configured for axially transporting the first vessel away from thevessel holder and then releasing the first vessel.

In a particular aspect of the invention, the method is for coating aninner surface of a restricted opening of a vessel, for example agenerally tubular vessel, by PECVD. The vessel includes an outersurface, an inner surface defining a lumen, a larger opening having aninner diameter, and a restricted opening that is defined by an innersurface and has an inner diameter smaller than the larger opening innerdiameter. A processing vessel is provided having a lumen and aprocessing vessel opening. The processing vessel opening is connectedwith the restricted opening of the vessel to establish communicationbetween the lumen of the vessel to be processed and the processingvessel lumen via the restricted opening. At least a partial vacuum isdrawn within the lumen of the vessel to be processed and the processingvessel lumen. A PECVD reactant is flowed through the first opening, thenthrough the lumen of the vessel to be processed, then through therestricted opening, then into the processing vessel lumen. Plasma isgenerated adjacent to the restricted opening under conditions effectiveto deposit a coating of a PECVD reaction product on the inner surface ofthe restricted opening.

Coated Vessel and Vessel Parts

The present invention further provides the coating resulting from themethod as described above, a surface coated with said coating, and avessel coated with said coating.

The surface coated with the coating, e.g. the vessel wall or a partthereof, may be glass or a polymer, preferably a thermoplastic polymer,more preferably a polymer selected from the group consisting of apolycarbonate, an olefin polymer, a cyclic olefin copolymer and apolyester. For example, it is a cyclic olefin copolymer (COC), apolyethylene terephthalate or a polypropylene. For syringe barrels, COCis particularly considered.

In a particular aspect of the invention, the vessel wall has an interiorpolymer layer enclosed by at least one exterior polymer layer. Thepolymers may be same or different. E.g., one of the polymer layers of acyclic olefin copolymer (COC) resin (e.g., defining a water vaporbarrier), another polymer layer is a layer of a polyester resin. Suchvessel may be made by a process including introducing COC and polyesterresin layers into an injection mold through concentric injectionnozzles.

The coated vessel of the invention may be empty, evacuated or(pre)filled with a compound or composition.

A particular aspect of the invention is a vessel having a passivatingcoating, for example a hydrophobic coating as defined above.

A further particular aspect of the invention is a surface having alubricity coating as defined above. It may be a vessel having thelubricity coating on a wall, preferably on the interior wall, e.g. asyringe barrel, or a vessel part or vessel cap having said coating onthe vessel contacting surface, e.g. a syringe plunger or a vessel cap.

A particular aspect of the invention is a syringe including a plunger, asyringe barrel, and a lubricity coating as defined above on either oneor both of these syringe parts, preferably on the inside wall of thesyringe barrel. The syringe barrel includes a barrel having an interiorsurface slidably receiving the plunger. The lubricity coating may bedisposed on the interior surface of the syringe barrel, or on theplunger surface contacting the barrel, or on both said surfaces. Thelubricity coating is effective to reduce the breakout force or theplunger sliding force necessary to move the plunger within the barrel.

A further particular aspect of the invention is a syringe barrel coatedwith the lubricity coating as defined in the preceding paragraph.

In a specific aspect of said coated syringe barrel, the syringe barrelcomprises a barrel defining a lumen and having an interior surfaceslidably receiving a plunger. The syringe barrel is advantageously madeof thermoplastic material. A lubricity coating is applied to the barrelinterior surface, the plunger, or both, by plasma-enhanced chemicalvapor deposition (PECVD). A solute retainer is applied over thelubricity coating by surface treatment, e.g. in an amount effective toreduce a leaching of the lubricity coating, the thermoplastic material,or both into the lumen. The lubricity coating and solute retainer arecomposed, and present in relative amounts, effective to provide abreakout force, plunger sliding force, or both that is less than thecorresponding force required in the absence of the lubricity coating andsolute retainer.

Still another aspect of the invention is a syringe including a plunger,syringe barrel, and interior and exterior coatings. The barrel has aninterior surface slidably receiving the plunger and an exterior surface.A lubricity coating is on the interior surface, and an additionalbarrier coating of SiO_(x), in which x is from about 1.5 to about 2.9,may be provided on the interior surface of the barrel. A barriercoating, e.g. of a resin or of a further SiO_(x) coating, mayadditionally be provided on the exterior surface of the barrel.

Another aspect of the invention is a syringe including a plunger, asyringe barrel, and a staked needle (a “staked needle syringe”). Theneedle is hollow with a typical size ranging from 18-29 gauge. Thesyringe barrel has an interior surface slidably receiving the plunger.The staked needle may be affixed to the syringe during the injectionmolding of the syringe or may be assembled to the formed syringe usingan adhesive. A cover is placed over the staked needle to seal thesyringe assembly. The syringe assembly must be sealed so that a vacuumcan be maintained within the syringe to enable the PECVD coatingprocess. Such syringes with staked needles are described in US XX[Please insert US provisional filing no.].

Another aspect of the invention is a syringe including a plunger, asyringe barrel, and a Luer fitting. The syringe barrel has an interiorsurface slidably receiving the plunger. The Luer fitting includes a Luertaper having an internal passage defined by an internal surface. TheLuer fitting is formed as a separate piece from the syringe barrel andjoined to the syringe barrel by a coupling. The internal passage of theLuer taper has a barrier coating of SiO_(x), in which x is from about1.5 to about 2.9.

Another aspect of the invention is a plunger for a syringe, including apiston and a push rod. The piston has a front face, a generallycylindrical side face, and a back portion, the side face beingconfigured to movably seat within a syringe barrel. The plunger has alubricity coating according to the present invention on its side face.The push rod engages the back portion of the piston and is configuredfor advancing the piston in a syringe barrel. The plunger mayadditionally comprise a SiO_(x) coating.

A further aspect of the invention is a vessel with just one opening,i.e. a vessel for collecting or storing a compound or composition. Suchvessel is in a specific aspect a tube, e.g. a sample collecting tube,e.g., a blood collecting tube. Said tube may be closed with a closure,e.g. a cap or stopper. Such cap or stopper may comprise a lubricitycoating according to the present invention on its surface which is incontact with the tube, and/or it may contain a passivating coatingaccording to the present invention on its surface facing the lumen ofthe tube. In a specific aspect, such stopper or a part thereof may bemade from an elastomeric material.

Such a stopper may be made as follows: The stopper is located in asubstantially evacuated chamber. A reaction mixture is providedincluding an organosilicon compound gas, optionally an oxidizing gas,and optionally a hydrocarbon gas. Plasma is formed in the reactionmixture, which is contacted with the stopper. A coating is deposited onat least a portion of the stopper.

A further aspect of the invention is a vessel having a barrier coatingaccording to the present invention. The vessel is generally tubular andmay be made of thermoplastic material. The vessel has a mouth and alumen bounded at least in part by a wall. The wall has an inner surfaceinterfacing with the lumen. In a preferred aspect, an at leastessentially continuous barrier coating made of SiO_(x) as defined aboveis applied on the inner surface of the wall. The barrier coating iseffective to maintain within the vessel at least 90% of its initialvacuum level, optionally 95% of its initial vacuum level, for a shelflife of at least 24 months. A closure is provided covering the mouth ofthe vessel and isolating the lumen of the vessel from ambient air.

The PECVD made coatings and PECVD coating methods using an organosiliconprecursor described in this specification are also useful for coatingcatheters or cuvettes to form a barrier coating, a hydrophobic coating,a lubricity coating, or more than one of these. A cuvette is a smalltube of circular or square cross section, sealed at one end, made of apolymer, glass, or fused quartz (for UV light) and designed to holdsamples for spectroscopic experiments. The best cuvettes are as clear aspossible, without impurities that might affect a spectroscopic reading.Like a test tube, a cuvette may be open to the atmosphere or have a capto seal it shut. The PECVD-applied coatings of the present invention canbe very thin, transparent, and optically flat, thus not interfering withoptical testing of the cuvette or its contents.

(Pre)Filled Coated Vessel

A specific aspect of the invention is a coated vessel as described abovewhich is prefilled or used for being filled with a compound orcomposition in its lumen. Said compound or composition may be

-   (i) a biologically active compound or composition, preferably a    medicament, more preferably insulin or a composition comprising    insulin; or-   (ii) a biological fluid, preferably a bodily fluid, more preferably    blood or a blood fraction (e.g. blood cells); or-   (iii) a compound or composition for combination with another    compound or composition directly in the vessel, e.g. a compound for    the prevention of blood clotting or platelet activation in a blood    collection tube, like citrate or a citrate containing composition.

Generally, the coated vessel of the present invention is particularlyuseful for collecting or storing a compound or composition which issensitive to mechanical and/or chemical effects of the surface of theuncoated vessel material, preferably for preventing or reducingprecipitation and/or clotting or platelet activation of a compound or acomponent of the composition in contact with the interior surface of thevessel.

.g., a cell preparation tube having a wall provided with a hydrophobiccoating of the present invention and containing an aqueous sodiumcitrate reagent is suitable for collecting blood and preventing orreducing blood coagulation. The aqueous sodium citrate reagent isdisposed in the lumen of the tube in an amount effective to inhibitcoagulation of blood introduced into the tube.

A specific aspect of the invention is a vessel for collecting/receivingblood or a blood containing vessel. The vessel has a wall; the wall hasan inner surface defining a lumen. The inner surface of the wall has anat least partial hydrophobic coating of the present invention. Thecoating can be as thin as monomolecular thickness or as thick as about1000 nm (on average or throughout the coating). The blood collected orstored in the vessel is preferably viable for return to the vascularsystem of a patient disposed within the lumen in contact with thecoating. The coating is effective to reduce the clotting or plateletactivation of blood exposed to the inner surface, compared to the sametype of wall uncoated.

Another aspect of the invention is an insulin containing vesselincluding a wall having an inner surface defining a lumen. The innersurface has an at least partial hydrophobic coating of the presentinvention. The coating can be from monomolecular thickness to about 1000nm thick (on average or throughout the coating) on the inner surface.Insulin or a composition comprising insulin is disposed within the lumenin contact with the coating. Optionally, the coating is effective toreduce the formation of a precipitate from insulin contacting the innersurface, compared to the same surface absent the coating.

A particular aspect of the invention is a prefilled syringe, e.g. asyringe prefilled with a medicament, a diagnostic compound orcomposition, or any other biologically of chemically active compound orcomposition which is intended to be dispensed using the syringe.

The present invention thus provides the following embodiments withregard to coating methods, coated products and use of said products:

1. A method for preparing a lubricity coating on a plastic substrate,the method comprising the steps

(a) providing a gas comprising an organosilicon precursor, andoptionally O₂, and optionally a noble gas, in the vicinity of thesubstrate surface; and

(b) generating a plasma in the gas, thus forming a coating on thesubstrate surface by plasma enhanced chemical vapor deposition (PECVD).

2. The method of (1), wherein the organosilicon precursor is amonocyclic siloxane, preferably is OMCTS.

3. The method according to any one of (1) to (2), wherein O₂ is present,preferably in a volume-volume ratio to the organosilicon precursor offrom 0:1 to 0.5:1, optionally from 0.01:1 to 0.5:1.

4. The method according to any one of (1) to (3), wherein Ar is presentas the noble gas.

5. The method according to any of the preceding, wherein the gascomprises from 1 to 6 standard volumes of the organosilicon precursor,from 1 to 100 standard volumes of the noble gas, and from 0.1 to 2standard volumes of O₂.

6. The method according to any one of the preceding, wherein both Ar andO₂ are present.

7. The method according to any one of the preceding wherein the plasmais generated with an electric power of from 0.1 to 25 W, preferably offrom 2 to 4 W; and/or

(ii) wherein the ratio of the electrode power to the plasma volume isless than 10 W/ml, preferably from 6 W/ml to 0.1 W/ml.

8. The method according to any one of the preceding, wherein theresulting coating has a roughness when determined by AFM and expressedas RMS of from more than 0 to 25 nm, preferably from 7 to 20 nm,optionally from 10 to 20 nm, optionally from 13 to 17 nm, optionallyfrom 13 to 15 nm.

9. The method according to any one of the preceding, additionallycomprising a step for preparing a barrier coating on the substratebefore the lubricity coating is applied, the additional step comprisingthe steps

(a) providing a gas comprising an organosilicon precursor and O₂ in thevicinity of the substrate surface; and

(b) generating a plasma from the gas, thus forming a SiOx barriercoating on the substrate surface by plasma enhanced chemical vapordeposition (PECVD).

10. The method according to (9) wherein in the step for preparing abarrier coating

(i) the plasma is generated with electrodes powered with sufficientpower to form a SiOx barrier coating on the substrate surface,preferably with electrodes supplied with an electric power of from 8 to500 W, preferably from 20 to 400 W, more preferably from 35 to 350 W,even more preferably of from 44 to 300 W, most preferably of from 44 to70 W; and/or

(ii) the ratio of the electrode power to the plasma volume is equal ormore than 5 W/ml, preferably is from 6 W/ml to 150 W/ml, more preferablyis from 7 W/ml to 100 W/ml, most preferably from 7 W/ml to 20 W/ml;and/or

(iii) the O₂ is present in a volume:volume ratio of from 1:1 to 100:1 inrelation to the silicon containing precursor, preferably in a ratio offrom 5:1 to 30:1, more preferably in a ratio of from 10:1 to 20:1, evenmore preferably in a ratio of 15:1.

11. The method of (9) or (10), wherein the organosilicon precursor forthe barrier coating is a linear siloxane, preferably HMDSO.

12. The method according to any one of the preceding, wherein thesubstrate is a polymer selected from the group consisting of apolycarbonate, an olefin polymer, a cyclic olefin copolymer and apolyester, and preferably is a cyclic olefin copolymer, a polyethyleneterephthalate or a polypropylene, and more preferably is COC.

13. The method according to any one of the preceding, wherein the plasmais generated with electrodes powered at a radiofrequency, preferably at13.56 MHz.

14. The method according to any one of the preceding, wherein theresulting lubricity coating has an atomic ratio SiwOxCy or SiwNxCywherein w is 1, x is from about 0.5 to about 2.4, y is from about 0.6 toabout 3.

15. A coated substrate coated with a lubricity coating which isobtainable by the method according to any one of the preceding and hasthe characteristics has defined in any one of the preceding.

16. The coated substrate according to (15), wherein the lubricitycoating has a lower frictional resistance than the uncoated surface,wherein preferably the frictional resistance is reduced by at least 25%,more preferably by at least 45%, even more preferably by at least 60% incomparison to the uncoated surface.

17. The coated substrate according to (15) or (16), additionallycomprising at least one layer of SiOx, wherein x is from 1.5 to 2.9,wherein

(i) the lubricity coating is situated between the SiOx layer and thesubstrate surface or vice versa, or wherein

(ii) the lubricity coating is situated between two SiOx layers or viceversa, or wherein

(iii) the layers of SiOx and the lubricity coating are a gradedcomposite of SiwOxCyHz to SiOx or vice versa.

18. The coated substrate according to (17), wherein the SiOx barriercoating has a thickness of from 20 to 30 nm and the lubricity coatinghas an average thickness of from 1 to 5000 nm, preferably of from 30 to1000 nm, more preferably of from 80 to 150 nm.

19. The coated substrate according to any one of (15) to (18), whereinthe lubricity coating

(i) has a lower wetting tension than the uncoated surface, preferably awetting tension of from 20 to 72 dyne/cm, more preferably a wettingtension of from 30 to 60 dynes/cm, more preferably a wetting tension offrom 30 to 40 dynes/cm, preferably 34 dyne/cm; and/or

(iv) is more hydrophobic than the uncoated surface.

20. A vessel coated on at least part of its interior surface, thusforming a coated substrate according to any one of (15) to (19),preferably a vessel which is

(i) a sample collection tube, in particular a blood collection tube; or

(ii) a vial; or

(iii) a syringe or a syringe part, in particular a syringe barrel or asyringe plunger or a syringe piston; or

(iv) a pipe; or

(v) a cuvette.

21. The coated vessel according to (20) which contains a compound orcomposition in its lumen, preferably a biologically active compound orcomposition or a biological fluid, more preferably (i) citrate or acitrate containing composition, (ii) a medicament, in particular insulinor an insulin containing composition, or (iii) blood or blood cells.

22. The coated vessel according to (20) or (21), which is a syringecomprising a barrel having an inner surface, a piston or plunger havingan outer surface engaging the inner surface of the barrel, wherein atleast one of said inner surface and outer surface is a coated substrateaccording to any one of (15) to (19).

23. The syringe of (22), wherein the plunger initation force Fi is from2.5 to 5 lbs and the plunger maintenance force Fm is from 2.5 to 8 lbs.

24. The syringe of (22) or (23), wherein the lubricity coating has theatomic ratio SiwOxCy or SiwNxCy wherein w is 1, x is from about 0.5 toabout 2.4, y is from about 0.6 to about 3.

25. The syringe of any one of (22) to (24), wherein the lubricitycoating has an average thickness of from 10 to 1000 nm.

26. The syringe of any one of (22) to (25), which is in total or in oneor more of its syringe parts made according to the method according toany one of (1) to (14), wherein the plastic substrate is COC, whereinthe gas in step (a) comprises octamethylcyclotetrasiloxane, O2 and Ar,and wherein the power for generating the plasma is from 6 W/ml to 0.1W/ml in relation to the volume of the syringe lumen.

27. The syringe according to any one of (22) to (26), which contains acompound or composition in its lumen, preferably a biologically activecompound or composition or a biological fluid, more preferably (i)citrate or a citrate containing composition, (ii) a medicament, inparticular insulin or an insulin containing composition, or (iii) bloodor blood cells.

28. A vessel processing system (20) for coating of a vessel (80), thesystem comprising a processing station arrangement (5501, 5502, 5503,5504, 5505, 5506, 70, 72, 74) configured for performing the method ofone of (1) to (14).

29. A computer-readable medium, in which a computer program for coatingof a vessel (80) is stored which, when being executed by a processor ofa vessel processing system (20), is adapted to instruct the processor tocontrol the vessel processing system such that it carries out the methodof one of (1) to (14).

30. A program element for coating of a vessel (80), which, when beingexecuted by a processor of a vessel processing system (20), is adaptedto instruct the processor to control the vessel processing system suchthat it carries out the method of one of (1) to (14).

A particular syringe barrel according to present invention which mayform part of a syringe is made according to the method of (1), whereinthe plastic substrate is COC, wherein the gas in step (a) comprisesoctamethylcyclotetrasiloxane, O2 and Ar, and wherein preferably thepower for generating the plasma is from 6 W/ml to 0.1 W/ml, in aparticular aspect from 0.8 to 1.3 W/ml in relation to the volume of thesyringe lumen.

An aspect of the invention is a method of applying a coating to asubstrate. The method includes providing a substrate; providing avaporizable organosilicon precursor; and applying the precursor to thesubstrate by chemical vapor deposition. The precursor is applied underconditions effective to form a coating. In a preferred aspect of theinvention, a gaseous reactant or process gas is employed having astandard volume ratio of from 1 to 6 standard volumes of the precursor,from 5 to 100 standard volumes of a carrier gas, and from 0.1 to 2standard volumes of an oxidizing agent.

Another aspect of the invention is a coating of the type made by theabove process.

Another aspect of the invention is a vessel including a lumen defined bya surface defining a substrate. A coating is present on at least aportion of the substrate. The coating is made by the previously definedprocess.

Still another aspect of the invention is a chemical vapor depositionapparatus for applying a coating to a substrate. The chemical vapordeposition apparatus includes a source of an organosilicon precursor, asource of a carrier gas, and a source of an oxidizing agent. Thechemical vapor deposition apparatus still further includes one or moreconduits for conveying to the substrate a gaseous reactant or processgas comprising from 1 to 6 standard volumes of the precursor, from 5 to100 standard volumes of the carrier gas, and from 0.1 to 2 standardvolumes of the oxidizing agent. The chemical vapor deposition apparatusfurther includes a source of microwave or radio frequency energy and anapplicator powered by the source of microwave or radio frequency energyfor generating plasma in the gaseous reactant or process gas.

Yet another aspect of the invention is a syringe comprising a plunger, abarrel, and a coating. The barrel is a vessel and has an interiorsurface defining the vessel lumen and receiving the plunger for sliding.The vessel interior surface is a substrate. The coating is a lubricitylayer or coating on the substrate, the plunger, or both, applied bychemical vapor deposition, employing as the gaseous reactant or processgas from 1 to 6 standard volumes of an organosilicon precursor, from 5to 100 standard volumes of a carrier gas, and from 0.1 to 2 standardvolumes of an oxidizing agent.

Even another aspect of the invention is a plunger for a syringe,comprising a piston, a coating, and a push rod. The piston has a frontface, a generally cylindrical side face comprising a substrate, and aback portion. The side face is configured to movably seat within asyringe barrel. The coating is on the substrate and is a lubricity layeror coating interfacing with the side face. The lubricity layer orcoating is produced from a chemical vapor deposition (CVD) processemploying the previously defined gaseous reactant or process gas. Thepush rod engages the back portion of the piston and is configured foradvancing the piston in a syringe barrel.

Another aspect of the invention is a stopper. The stopper includes asliding surface defining a substrate and adapted to be received in anopening to be stopped. The substrate has on it a lubricity coating madeby providing a precursor comprising an organosilicon compound; andapplying the precursor to at least a portion of the sliding surface bychemical vapor deposition, employing a gaseous reactant or process gasas defined above.

Even another aspect of the invention is a medical or diagnostic kitincluding a vessel having a coating as defined in any embodiment aboveon a substrate as defined in any embodiment above. Optionally, the kitadditionally includes a medicament or diagnostic agent which iscontained in the coated vessel in contact with the coating; and/or ahypodermic needle, double-ended needle, or other delivery conduit;and/or an instruction sheet.

Other aspects of the invention include any one or more of the following:

Use of the coating according to any embodiment described above forcoating a surface and thereby preventing or reducing mechanical and/orchemical effects of the surface on a compound or composition in contactwith the coating;

Use of the coating according to any described embodiment as a lubricitylayer;

Use of the coating according to any described embodiment for protectinga compound or composition contacting the coating against mechanicaland/or chemical effects of the surface of the uncoated vessel material;

Use of the coating according to any described embodiment for preventingor reducing precipitation and/or clotting or platelet activation of acompound or a component of the composition in contact with the coating.

As one option, the compound or a component of the composition isinsulin, and precipitation of the insulin is prevented or reduced. Asanother option, the compound or a component of the composition is bloodor a blood fraction, and blood clotting or platelet activation isprevented or reduced. As still another option, the coated vessel is ablood collection tube. Optionally, the blood collection tube can containan agent for preventing blood clotting or platelet activation, forexample ethylenediaminetetraacetic acid (EDTA), a sodium salt thereof,or heparin.

Additional options for use of the invention include any one or more ofthe following:

Use of a coated substrate according to any described embodiment forreception and/or storage and/or delivery of a compound or composition;

The use of a coated substrate according to any described embodiment forstoring insulin.

The use of a coated substrate according to any described embodiment forstoring blood. Optionally, the stored blood is viable for return to thevascular system of a patient.

Use of a coating according to any described embodiment as (i) alubricity layer or coating having a lower frictional resistance than theuncoated surface; and/or (ii) a hydrophobic layer or coating that ismore hydrophobic than the uncoated surface.

Other aspects of the invention will become apparent to a person ofordinary skill in the art after reviewing the present disclosure andclaims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic sectional view of a vessel holder in a coatingstation according to an embodiment of the disclosure.

FIG. 2 is a section taken along section lines A-A of FIG. 1.

FIGS. 3A, 3B, and 3C show the drawbacks of silicon oil (or any otheroil) as lubricant. Non-uniformity of silicon oil occurs because it isnot covalently bound to the surface and flows. A.) Silicon oil is pushedoff the syringe barrel wall by the plunger following insertion of theplunger B) Silicon oil is forced out of the area between the plunger andsyringe wall leading to high break loose forces. C.) Silicon oil flowsover time due to gravitational forces.

FIG. 4 is an exploded longitudinal sectional view of a syringe and capadapted for use as a prefilled syringe.

FIG. 5 is a perspective view of a blood collection tube assembly havinga closure according to still another embodiment of the invention.

FIG. 6 is a fragmentary section of the blood collection tube and closureassembly of FIG. 5.

FIG. 7 is an isolated section of an elastomeric insert of the closure ofFIGS. 5 and 6.

FIG. 8 is a view similar to FIG. 1 of another embodiment for processingsyringe barrels and other vessels.

FIG. 9 is an enlarged detail view of the processing vessel of FIG. 8.

FIG. 10 is an alternative construction for a vessel holder useful withany embodiment of the invention, for example those of the other Figures.

FIG. 11 is a schematic view of an assembly for treating vessels. Theassembly is usable with the apparatus in any of the preceding figures.

FIG. 12 shows a schematic representation of an exemplary vesselprocessing system.

FIG. 13 shows a schematic representation of an exemplary vesselprocessing system.

FIG. 14 shows a processing station of an exemplary vessel processingsystem.

FIG. 15 shows a portable vessel holder.

FIG. 16 shows a SEM image of Example P. The horizontal edge-to-edgescale is 5 μm.

FIG. 17 shows a SEM image of Example S. The horizontal edge-to-edgescale is 5 pm.

FIG. 18A shows the results of the AFM imaging performed on a firstportion of Example Q. A 10 μm×10 μm area was imaged. A top down view ofthe area is shown, together with the topography differences along afirst cross section indicated by the line drawn in the top down view.The vertical depth of the features was measured using the cross sectiontool. Results for the parameters measured, like RMS, Ra and Rmax areindicated in the top right box.

FIG. 18B is similar to FIG. 18A, but shows the results of the AFMimaging performed on Example Q along a second cross section indicated bythe line drawn in the top down view.

FIG. 18C is similar to FIG. 18A, but shows the results of the AFMimaging performed on Example Q along a third cross section indicated bythe line drawn in the top down view.

FIG. 19A is similar to FIG. 18A, but shows the results of the AFMimaging performed on Example T along a first cross section indicated bythe line drawn in the top down view.

FIG. 19B is similar to FIG. 19A, but shows the results of the AFMimaging performed on Example T along a second cross section indicated bythe line drawn in the top down view.

FIG. 19C is similar to FIG. 19A, but shows the results of the AFMimaging performed on Example T along a third cross section indicated bythe line drawn in the top down view.

FIG. 20A is similar to FIG. 18A, but shows the results of the AFMimaging performed on Example V along a first cross section indicated bythe line drawn in the top down view.

FIG. 20B is similar to FIG. 20A, but shows the results of the AFMimaging performed on Example V along a second cross section indicated bythe line drawn in the top down view.

FIG. 20C is similar to FIG. 20A, but shows the results of the AFMimaging performed on Example V along a third cross section indicated bythe line drawn in the top down view.

FIG. 21 shows a TEM image of a lubricity coating according to theinvention coated on a SiO₂ barrier coating, which in turn is coated on aCOC substrate.

FIG. 22 shows a TEM image of a SiO₂ barrier coating which is coated on aCOC substrate.

FIG. 23 shows the meniscus made by water in a.) glass tube, b.)hydrophilic SiO₂ coated COC tube, c.) hydrophobic Si_(w)O_(x)C_(y)H_(z)coated COC tube, and d.) uncoated COC tube. The hydrophilic SiO₂ coatedtube and borosilicate glass tube have a similar meniscus, demonstratingthat the hydrophilicity of the hydrophilic SiO₂ coating is comparable toa glass surface. The hydophobic coated tube and the uncoated COC tubeeach have a meniscus that is expected from a hydrophobic surface.

FIG. 24 is a longitudinal section of a syringe with a staked needle.

FIGS. 25A. 25B, an 25C are fragmentary longitudinal sections of thedispensing end of an alternative syringe with a staked needle.

FIG. 26 is a longitudinal section of an alternative syringe with astaked needle.

FIG. 27 is a diagrammatic view showing a flexible diaphragm 71144 towhich the needle is attached.

The following reference characters are used in the drawing figures:

20 Vessel processing system 28 Coating station 38 Vessel holder 50Vessel holder 70 Conveyor 72 Transfer mechanism (on) 74 Transfermechanism (off) 80 Vessel 82 Opening 84 Closed end 86 Wall 88 Interiorsurface 90 Barrier layer 92 Vessel port 94 Vacuum duct 96 Vacuum port 98Vacuum source 100 O-ring (of 92) 102 O-ring (of 96) 104 Gas inlet port106 O-ring (of 100) 108 Probe (counter electrode) 110 Gas delivery port(of 108) 114 Housing (of 50 or 112) 116 Collar 118 Exterior surface (of80) 144 PECVD gas source 152 Pressure gauge 160 Electrode 162 Powersupply 164 Sidewall (of 160) 166 Sidewall (of 160) 168 Closed end (of160) 200 Electrode 250 Syringe barrel 252 Syringe 254 Interior surface(of 250) 256 Back end (of 250) 258 Plunger (of 252) 260 Front end (of250) 262 Cap 264 Interior surface (of 262) 268 Vessel 270 Closure 272Interior facing surface 274 Lumen 276 Wall-contacting surface 278 Innersurface (of 280) 280 Vessel wall 282 Stopper 284 Shield 286 Lubricitylayer 288 Barrier layer 290 Apparatus for coating, for example, 250 292Inner surface (of 294) 294 Restricted opening (of 250) 296 Processingvessel 298 Outer surface (of 250) 300 Lumen (of 250) 302 Larger opening(of 250) 304 Processing vessel lumen 306 Processing vessel opening 308Inner electrode 310 Interior passage (of 308) 312 Proximal end (of 308)314 Distal end (of 308) 316 Distal opening (of 308) 318 Plasma 332 Firstfitting (male Luer taper) 334 Second fitting (female Luer taper) 336Locking collar (of 332) 338 First abutment (of 332) 340 Second abutment(of 332) 342 O-ring 344 Dog 408 Inner wall 410 Outer wall 482 Vesselholder body 484 Upper portion (of 482) 486 Base portion (of 482) 488Joint (between 484 and 486) 490 O-ring 492 Annular pocket 494 Radiallyextending abutment surface 496 Radially extending wall 498 Screw 500Screw 502 Vessel port 504 Second O-ring 506 Inner diameter (of 490) 508Vacuum duct (of 482) 574 Main vacuum valve 576 Vacuum line 578 Manualbypass valve 580 Bypass line 582 Vent valve 584 Main reactant gas valve586 Main reactant feed line 588 Organosilicon liquid reservoir 590Organosilicon feed line (capillary) 592 Organosilicon shut-off valve 594Oxygen tank 596 Oxygen feed line 598 Mass flow controller 600 Oxygenshut-off valve 614 Headspace 616 Pressure source 618 Pressure line 620Capillary connection 5501 First processing station 5502 Secondprocessing station 5503 Third processing station 5504 Fourth processingstation 5505 Processor 5506 User interface 5507 Bus 5701 PECVD apparatus5702 First detector 5703 Second detector 5704 Detector 5705 Detector5706 Detector 5707 Detector 7001 Conveyor exit branch 7002 Conveyor exitbranch 7003 Conveyor exit branch 7004 Conveyor exit branch 7120 Syringe7122 Needle 7124 Barrel 7126 Cap 7128 Barrier coating 7130 Lubricitycoating 7132 Outside surface 7134 Delivery outlet 7136 Base (of 22) 7138Internal passage 7140 Generally cylindrical interior surface portion7142 Generally hemispherical interior surface portion 7144 Front passage7146 Lumen 7148 Lumen 7150 Ambient air 7152 Rim 7154 Exterior portion(of 7124) 7156 Opening 7158 Fluid 7160 Material (of 7124) 7164Non-cylindrical portion (of 7122) 7166 Plunger 7168 Base 7170 Coupling7172 Flexible lip seal 7174 Detent 7176 Projection 7196 Internal portion(of 7126) 7198 External portion (of 7126) 71106 Rear passage (of barrel)71110 Tapered nose (of 7120) 71112 Tapered throat (of 7126) 71114 Collar(of syringe) 71116 Interior thread (of 71114) 71118 Dog (of 26) 71120Dog (of 26) 71122 Syringe barrel 71124 Syringe cap 71126 (Syringe cap(flexible) 71128 Cap-syringe interface 71130 Syringe barrel 71134Delivery outlet 71136 Base (of 22) 71140 Finger grip 71144 Flexiblediaphragm

DETAILED DESCRIPTION

The present invention will now be described more fully, inter alia withreference to the accompanying drawings, in which several embodiments areshown. This invention can, however, be embodied in many different formsand should not be construed as limited to the embodiments set forthhere. Rather, these embodiments are examples of the invention, which hasthe full scope indicated by the language of the claims. Like numbersrefer to like or corresponding elements throughout. The followingdisclosure relates to all embodiments unless specifically limited to acertain embodiment.

Definition Section

In the context of the present invention, the following definitions andabbreviations are used:

RF is radio frequency; sccm is standard cubic centimeters per minute.

The term “at least” in the context of the present invention means “equalor more” than the integer following the term. The word “comprising” doesnot exclude other elements or steps, and the indefinite article “a” or“an” does not exclude a plurality unless indicated otherwise. Whenever aparameter range is indicated, it is intended to disclose the parametervalues given as limits of the range and all values of the parameterfalling within said range.

“First” and “second” or similar references to, e.g., processing stationsor processing devices refer to the minimum number of processing stationsor devices that are present, but do not necessarily represent the orderor total number of processing stations and devices. These terms do notlimit the number of processing stations or the particular processingcarried out at the respective stations.

For purposes of the present invention, an “organosilicon precursor” is acompound having at least one of the linkage:

which is a tetravalent silicon atom connected to an oxygen or nitrogenatom and an organic carbon atom (an organic carbon atom being a carbonatom bonded to at least one hydrogen atom). A volatile organosiliconprecursor, defined as such a precursor that can be supplied as a vaporin a PECVD apparatus, is an optional organosilicon precursor.Optionally, the organosilicon precursor is selected from the groupconsisting of a linear siloxane, a monocyclic siloxane, a polycyclicsiloxane, a polysilsesquioxane, an alkyl trimethoxysilane, a linearsilazane, a monocyclic silazane, a polycyclic silazane, apolysilsesquiazane, and a combination of any two or more of theseprecursors.

The feed amounts of PECVD precursors, gaseous reactant or process gases,and carrier gas are sometimes expressed in “standard volumes” in thespecification and claims. The standard volume of a charge or other fixedamount of gas is the volume the fixed amount of the gas would occupy ata standard temperature and pressure (without regard to the actualtemperature and pressure of delivery). Standard volumes can be measuredusing different units of volume, and still be within the scope of thepresent disclosure and claims. For example, the same fixed amount of gascould be expressed as the number of standard cubic centimeters, thenumber of standard cubic meters, or the number of standard cubic feet.Standard volumes can also be defined using different standardtemperatures and pressures, and still be within the scope of the presentdisclosure and claims. For example, the standard temperature might be 0°C. and the standard pressure might be 760 Torr (as is conventional), orthe standard temperature might be 20° C. and the standard pressure mightbe 1 Torr. But whatever standard is used in a given case, when comparingrelative amounts of two or more different gases without specifyingparticular parameters, the same units of volume, standard temperature,and standard pressure are to be used relative to each gas, unlessotherwise indicated.

The corresponding feed rates of PECVD precursors, gaseous reactant orprocess gases, and carrier gas are expressed in standard volumes perunit of time in the specification. For example, in the working examplesthe flow rates are expressed as standard cubic centimeters per minute,abbreviated as sccm. As with the other parameters, other units of timecan be used, such as seconds or hours, but consistent parameters are tobe used when comparing the flow rates of two or more gases, unlessotherwise indicated.

A “vessel” in the context of the present invention can be any type ofvessel with at least one opening and a wall defining an interiorsurface. The substrate can be the inside wall of a vessel having alumen. Though the invention is not necessarily limited to vessels of aparticular volume, vessels are contemplated in which the lumen has avoid volume of from 0.5 to 50 mL, optionally from 1 to 10 mL, optionallyfrom 0.5 to 5 mL, optionally from 1 to 3 mL. The substrate surface canbe part or all of the inner surface of a vessel having at least oneopening and an inner surface.

The term “at least” in the context of the present invention means “equalor more” than the integer following the term. Thus, a vessel in thecontext of the present invention has one or more openings. One or twoopenings, like the openings of a sample tube (one opening) or a syringebarrel (two openings) are preferred. If the vessel has two openings,they can be of same or different size. If there is more than oneopening, one opening can be used for the gas inlet for a PECVD coatingmethod according to the present invention, while the other openings areeither capped or open. A vessel according to the present invention canbe a sample tube, e.g. for collecting or storing biological fluids likeblood or urine, a syringe (or a part thereof, for example a syringebarrel) for storing or delivering a biologically active compound orcomposition, e.g. a medicament or pharmaceutical composition, a vial forstoring biological materials or biologically active compounds orcompositions, a pipe, e.g. a catheter for transporting biologicalmaterials or biologically active compounds or compositions, or a cuvettefor holding fluids, e.g. for holding biological materials orbiologically active compounds or compositions.

A vessel can be of any shape, a vessel having a substantiallycylindrical wall adjacent to at least one of its open ends beingpreferred. Generally, the interior wall of the vessel is cylindricallyshaped, like, e.g. in a sample tube or a syringe barrel. Sample tubesand syringes or their parts (for example syringe barrels) arecontemplated.

A “hydrophobic layer” in the context of the present invention means thatthe coating lowers the wetting tension of a surface coated with thecoating, compared to the corresponding uncoated surface. Hydrophobicityis thus a function of both the uncoated substrate and the coating. Thesame applies with appropriate alterations for other contexts wherein theterm “hydrophobic” is used. The term “hydrophilic” means the opposite,i.e. that the wetting tension is increased compared to reference sample.The present hydrophobic layers are primarily defined by theirhydrophobicity and the process conditions providing hydrophobicity, andoptionally can have a composition according to the empirical compositionor sum formula Si_(w)O_(x)C_(y)H_(z). It generally has an atomic ratioSi_(w)O_(x)C_(y) wherein w is 1, x is from about 0.5 to about 2.4, y isfrom about 0.6 to about 3, preferably w is 1, x is from about 0.5 to1.5, and y is from 0.9 to 2.0, more preferably w is 1, x is from 0.7 to1.2 and y is from 0.9 to 2.0. The atomic ratio can be determined by XPS(X-ray photoelectron spectroscopy). Taking into account the H atoms, thecoating may thus in one aspect have the formula Si_(w)O_(x)C_(y)H_(z),for example where w is 1, x is from about 0.5 to about 2.4, y is fromabout 0.6 to about 3, and z is from about 2 to about 9. Typically, theatomic ratios are Si 100: O 80-110: C 100-150 in a particular coating ofpresent invention. Specifically, the atomic ratio may be Si 100: O92-107: C 116-133, and such coating would hence contain 36% to 41%carbon normalized to 100% carbon plus oxygen plus silicon.

These values of w, x, y, and z are applicable to the empiricalcomposition Si_(w)O_(x)C_(y)H_(z) throughout this specification. Thevalues of w, x, y, and z used throughout this specification should beunderstood as ratios or an empirical formula (e.g. for a coating),rather than as a limit on the number or type of atoms in a molecule. Forexample, octamethylcyclotetrasiloxane, which has the molecularcomposition Si₄O₄C₈H₂₄, can be described by the following empiricalformula, arrived at by dividing each of w, x, y, and z in the molecularformula by 4, the largest common factor: Si₁O₁C₂H₆. The values of w, x,y, and z are also not limited to integers. For example, (acyclic)octamethyltrisiloxane, molecular composition Si₃O₂C₈H₂₄, is reducible toSi₁O_(0.67)C_(2.67)H₈.

“Wetting tension” is a specific measure for the hydrophobicity orhydrophilicity of a surface. An optional wetting tension measurementmethod in the context of the present invention is ASTM D 2578 or amodification of the method described in ASTM D 2578. This method usesstandard wetting tension solutions (called dyne solutions) to determinethe solution that comes nearest to wetting a plastic film surface forexactly two seconds. This is the film's wetting tension. The procedureutilized is varied herein from ASTM D 2578 in that the substrates arenot flat plastic films, but are tubes made according to the Protocol forForming PET Tube and (except for controls) coated according to theProtocol for Coating Tube Interior with Hydrophobic Layer or coating(see Example 9 of EP2251671 A2).

A “lubricity layer” according to the present invention is a coatingwhich has a lower frictional resistance than the uncoated surface. Inother words, it reduces the frictional resistance of the coated surfacein comparison to a reference surface that is uncoated. The presentlubricity layers are primarily defined by their lower frictionalresistance than the uncoated surface and the process conditionsproviding lower frictional resistance than the uncoated surface, andoptionally can have a composition according to the empirical compositionSi_(w)O_(x)C_(y)H_(z), as defined herein. It generally has an atomicratio Si_(w)O_(x)C_(y) wherein w is 1, x is from about 0.5 to about 2.4,y is from about 0.6 to about 3, preferably w is 1, x is from about 0.5to 1.5, and y is from 0.9 to 2.0, more preferably w is 1, x is from 0.7to 1.2 and y is from 0.9 to 2.0. The atomic ratio can be determined byXPS (X-ray photoelectron spectroscopy). Taking into account the H atoms,the coating may thus in one aspect have the formulaSi_(w)O_(x)C_(y)H_(z), for example where w is 1, x is from about 0.5 toabout 2.4, y is from about 0.6 to about 3, and z is from about 2 toabout 9. Typically, the atomic ratios are Si 100: O 80-110: C 100-150 ina particular coating of present invention. Specifically, the atomicratio may be Si 100: O 92-107: C 116-133, and such coating would hencecontain 36% to 41% carbon normalized to 100% carbon plus oxygen plussilicon.

“Frictional resistance” can be static frictional resistance and/orkinetic frictional resistance.

One of the optional embodiments of the present invention is a syringepart, e.g. a syringe barrel or plunger, coated with a lubricity layer.In this contemplated embodiment, the relevant static frictionalresistance in the context of the present invention is the breakout forceas defined herein, and the relevant kinetic frictional resistance in thecontext of the present invention is the plunger sliding force as definedherein. For example, the plunger sliding force as defined and determinedherein is suitable to determine the presence or absence and thelubricity characteristics of a lubricity layer or coating in the contextof the present invention whenever the coating is applied to any syringeor syringe part, for example to the inner wall of a syringe barrel. Thebreakout force is of particular relevance for evaluation of the coatingeffect on a prefilled syringe, i.e. a syringe which is filled aftercoating and can be stored for some time, e.g. several months or evenyears, before the plunger is moved again (has to be “broken out”).

The “plunger sliding force” (synonym to “glide force”, “maintenanceforce”, Fm, also used in this description) in the context of the presentinvention is the force required to maintain movement of a plunger in asyringe barrel, e.g. during aspiration or dispense. It canadvantageously be determined using the ISO 7886-1:1993 test describedherein and known in the art. A synonym for “plunger sliding force” oftenused in the art is “plunger force” or “pushing force”.

The “plunger breakout force” (synonym to “breakout force”, “break looseforce”, “initation force”, Fi, also used in this description) in thecontext of the present invention is the initial force required to movethe plunger in a syringe, for example in a prefilled syringe.

Both “plunger sliding force” and “plunger breakout force” and methodsfor their measurement are described in more detail in subsequent partsof this description. These two forces can be expressed in N, lbs or kgand all three units are used herein. These units correlate as follows:1N=0.102 kg=0.2248 lbs (pounds).

Sliding force and breakout force are sometimes used herein to describethe forces required to advance a stopper or other closure into a vessel,such as a medical sample tube or a vial, to seat the stopper in a vesselto close the vessel. Its use is analogous to use in the context of asyringe and its plunger, and the measurement of these forces for avessel and its closure are contemplated to be analogous to themeasurement of these forces for a syringe, except that at least in mostcases no liquid is ejected from a vessel when advancing the closure to aseated position.

“Slidably” means that the plunger, closure, or other removable part ispermitted to slide in a syringe barrel or other vessel.

In the context of this invention, “substantially rigid” means that theassembled components (ports, duct, and housing, explained further below)can be moved as a unit by handling the housing, without significantdisplacement of any of the assembled components respecting the others.Specifically, none of the components are connected by hoses or the likethat allow substantial relative movement among the parts in normal use.The provision of a substantially rigid relation of these parts allowsthe location of the vessel seated on the vessel holder to be nearly aswell known and precise as the locations of these parts secured to thehousing.

Description Section

An embodiment of the present invention is a method of applying a coatingsuch as 90 to a substrate such as the vessel 80 (FIG. 1), the vessel 268(FIG. 6), the stopper 282 (FIGS. 6-7), or the syringe 252 (FIG. 4). Themethod can be used with any disclosed embodiment. The method includesproviding a substrate, for example any of those mentioned above;providing a vaporizable organosilicon precursor, for example any ofthose disclosed in this specification; and applying the precursor to thesubstrate by chemical vapor deposition. The precursor is applied, forexample in the apparatus of FIG. 2, 26, of the EP applications cited inparagraph [002], or of any other embodiment, under conditions effectiveto form a coating.

A gaseous reactant or process gas can be employed having a standardvolume ratio of, for example when a lubricity coating is prepared:

-   -   from 1 to 6 standard volumes, optionally from 2 to 4 standard        volumes, optionally equal to or less than 6 standard volumes,        optionally equal to or less than 2.5 standard volumes,        optionally equal to or less than 1.5 standard volumes,        optionally equal to or less than 1.25 standard volumes of the        precursor;    -   from 1 to 100 standard volumes, optionally from 5 to 100        standard volumes, optionally from 10 to 70 standard volumes, of        a carrier gas;    -   from 0.1 to 2 tandard volumes, optionally from 0.2 to 1.5        standard volumes, optionally from 0.2 to 1 standard volumes,        optionally from 0.5 to 1.5 standard volumes, optionally from 0.8        to 1.2 standard volumes of an oxidizing agent.

Another embodiment is a coating, for example 286 in FIG. 7 or acomparable coating in any embodiment, of the type made by the aboveprocess.

Another embodiment is a vessel such as the vessel 80 (FIG. 1), thevessel 268 (FIG. 6), or the syringe 252 (FIG. 4) including a lumendefined by a surface defining a substrate. A coating is present on atleast a portion of the substrate. The coating is made by the previouslydefined process.

Still another embodiment is a chemical vapor deposition apparatus suchas the apparatus 28 illustrated in FIG. 11 (or any other illustratedcoating apparatus, such as the apparatus illustrated in FIG. 1, 2, 8,10, or 12-15), for applying a coating to a substrate.

FIG. 12 shows a vessel processing system 20 according to an exemplaryembodiment of the present invention. The vessel processing system 20comprises, inter alia, a first processing station 5501 and may or maynot also comprise a second processing station 5502. An example for suchprocessing stations is for example depicted in FIG. 1, reference numeral28.

The first vessel processing station 5501 contains a vessel holder 38which holds a seated vessel 80. Although FIG. 12 depicts a blood tube80, the vessel may also be a syringe body, a vial, a catheter or, forexample, a pipette. The vessel may, for example, be made of glass orplastic. In case of plastic vessels, the first processing station mayalso comprise a mould for moulding the plastic vessel.

After the first processing at the first processing station (whichprocessing may comprise moulding of the vessel, a first inspection ofthe vessel for defects, coating of the interior surface of the vesseland a second inspection of the vessel for defects, in particular of theinterior coating), the vessel holder 38 may be transported together withthe vessel 82 to the second vessel processing station 5502. Thistransportation is performed by a conveyor arrangement 70, 72, 74. Forexample, a gripper or several grippers may be provided for gripping thevessel holder 38 and/or the vessel 80 in order to move the vessel/holdercombination to the next processing station 5502. Alternatively, only thevessel may be moved without the holder. However, it may be advantageousto move the holder together with the vessel in which case the holder isadapted such that it can be transported by the conveyor arrangement.

FIG. 13 shows a vessel processing system 20 according to anotherexemplary embodiment of the present invention. Again, two vesselprocessing stations 5501, 5502 are provided. Furthermore, additionalvessel processing stations 5503, 5504 may be provided which are arrangedin series and in which the vessel can be processed, i.e. inspectedand/or coated.

A vessel can be moved from a stock to the left processing station 5504.Alternatively, the vessel can be moulded in the first processing station5504. In any case, a first vessel processing is performed in theprocessing station 5504, such as a moulding, an inspection and/or acoating, which may be followed by a second inspection. Then, the vesselis moved to the next processing station 5501 via the conveyorarrangement 70, 72, 74. Typically, the vessel is moved together with thevessel holder. A second processing is performed in the second processingstation 5501 after which the vessel and holder are moved to the nextprocessing station 5502 in which a third processing is performed. Thevessel is then moved (again together with the holder) to the fourthprocessing station 5503 for a fourth processing, after which it isconveyed to a storage.

Before and after each coating step or moulding step or any other stepwhich manipulates the vessel an inspection of the whole vessel, of partof the vessel and in particular of an interior surface of the vessel maybe performed. The result of each inspection can be transferred to acentral processing unit 5505 via a data bus 5507. Each processingstation is connected to the data bus 5507. The above described programelement may run on the processor 5505, and the processor, which may beadapted in form of a central control and regulation unit, controls thesystem and may also be adapted to process the inspection data, toanalyze the data and to determine whether the last processing step wassuccessful.

If it is determined that the last processing step was not successful,because for example the coating comprises holes or because the surfaceof the coating is determined to be regular or not smooth enough, thevessel does not enter the next processing station but is either removedfrom the production process (see conveyor sections 7001, 7002, 7003,7004) or conveyed back in order to become re-processed.

The processor 5505 may be connected to a user interface 5506 forinputting control or regulation parameters.

FIG. 14 shows a vessel processing station 5501 according to an exemplaryembodiment of the present invention. The station comprises a PECVDapparatus 5701 for coating an interior surface of the vessel.Furthermore, several detectors 5702-5707 may be provided for vesselinspection. Such detectors may for example be electrodes for performingelectric measurements, optical detectors, like CCD cameras, gasdetectors or pressure detectors.

FIG. 15 shows a vessel holder 38 according to an exemplary embodiment ofthe present invention, together with several detectors 5702, 5703, 5704and an electrode with gas inlet port 108, 110.

The electrode and the detector 5702 may be adapted to be moved into theinterior space of the vessel 80 when the vessel is seated on the holder38.

The optical inspection may be particularly performed during a coatingstep, for example with the help of optical detectors 5703, 5704 whichare arranged outside the seated vessel 80 or even with the help of anoptical detector 5705 arranged inside the interior space of the vessel80.

The detectors may comprise colour filters such that differentwavelengths can be detected during the coating process. The processingunit 5505 analyzes the optical data and determines whether the coatingwas successful or not to a predetermined level of certainty. If it isdetermined that the coating was most probably unsuccessful, therespective vessel is separated from the processing system orre-processed.

Referring now to FIG. 11, the chemical vapor deposition apparatusincludes a source of an organosilicon precursor such as the reservoir588, a source of a carrier gas such as 602, and a source of an oxidizingagent such as 594. The chemical vapor deposition apparatus still furtherincludes one or more conduits, such as the conduits 108, 586, 590, 604,and 596, for conveying to the substrate a gaseous reactant or processgas comprising from 1 to 6 standard volumes of the precursor, from 5 to100 standard volumes of the carrier gas, and from 0.1 to 2 standardvolumes of the oxidizing agent. The chemical vapor deposition apparatusfurther includes a source 162 of microwave or radio frequency energy andan applicator or electrode such as 160 powered by the source ofmicrowave or radio frequency energy for generating plasma in the gaseousreactant or process gas.

Yet another embodiment is a syringe such as 252 comprising a plunger258, a barrel 250, and a coating on the interior surface 264. The barrel250 is a vessel and has an interior surface 264 defining the vessellumen 274 and receiving the plunger 258 for sliding. The vessel interiorsurface 264 is a substrate. The coating is a lubricity layer on thesubstrate 264, the plunger 258, or both, applied by chemical vapordeposition, employing as the gaseous reactant or process gas from 1 to 6standard volumes of an organosilicon precursor, from 5 to 100 standardvolumes of a carrier gas, and from 0.1 to 2 standard volumes of anoxidizing agent. In addition to this lubricity coating, the syringe maycontain one or more other coatings, e.g. a SiO_(x) barrier coating asdescribed herein. Said additional coating(s) may be located under orover the lubricity coating, i.e. nearer to the coated substrate ornearer to the lumen of the syringe.

A concern of converting from glass to plastic syringes centers aroundthe potential for leachable materials from plastics. With plasma coatingtechnology, the coating, being derived from non-metal gaseous precursorse.g. HMDSO, will itself contain no trace metals and function as abarrier to inorganic, metals and organic solutes, preventing leaching ofthese species from the coated substrate into syringe fluids. In additionto leaching control of plastic syringes, the same plasma coatingtechnology offers potential to provide a solute barrier to the plungertip, typically made of elastomeric plastic compositions containing evenhigher levels of leachable organic oligomers and catalysts.

Moreover, certain syringes prefilled with synthetic and biologicalpharmaceutical formulations are very oxygen and moisture sensitive. Acritical factor in the conversion from glass to plastic syringe barrelswill be the improvement of plastic oxygen and moisture barrierperformance. The plasma coating technology is suitable to provide aSiO_(x) barrier coating for protection against oxygen and moisture.

Even another embodiment is a plunger 258 for a syringe 252, comprising apiston or tip, a coating, and a push rod. The piston or tip has a frontface, a generally cylindrical side face that slides within the barrel250, comprising a substrate, and a back portion. The side face isconfigured to movably seat within a syringe barrel. The coating is onthe substrate and is a lubricity layer interfacing with the side face.The lubricity layer is produced from a chemical vapor deposition (CVD)process employing the previously defined gaseous reactant or processgas. The push rod engages the back portion of the piston and isconfigured for advancing the piston in a syringe barrel.

Another embodiment is a stopper such as 282 (FIGS. 6-7). The stopper 282includes a sliding surface 276 defining a substrate and adapted to bereceived in an opening to be stopped. The substrate has on it alubricity coating 288 made by providing a precursor comprising anorganosilicon compound and applying the precursor to at least a portionof the sliding surface by chemical vapor deposition, employing a gaseousreactant or process gas as defined above.

Even another embodiment is a medical or diagnostic kit including avessel having a coating as defined in any embodiment above on asubstrate as defined in any embodiment above. Optionally, the kitadditionally includes a medicament or diagnostic agent which iscontained in the coated vessel in contact with the coating; and/or ahypodermic needle, double-ended needle, or other delivery conduit;and/or an instruction sheet.

Other aspects of the invention include any one or more of the following:

Use of the coating according to any embodiment described above forcoating a surface and thereby preventing or reducing mechanical and/orchemical effects of the surface on a compound or composition in contactwith the coating;

Use of the coating according to any described embodiment as a lubricitylayer;

Use of the coating according to any described embodiment for protectinga compound or composition contacting the coating against mechanicaland/or chemical effects of the surface of the uncoated vessel material;

Use of the coating according to any described embodiment for preventingor reducing precipitation and/or clotting or platelet activation of acompound or a component of the composition in contact with the coating.

As one option, the compound or a component of the composition isinsulin, and precipitation of the insulin is prevented or reduced. Asanother option, the compound or a component of the composition is bloodor a blood fraction, and blood clotting or platelet activation isprevented or reduced. As still another option, the coated vessel is ablood collection tube. Optionally, the blood collection tube can containan agent for preventing blood clotting or platelet activation, forexample ethylenediamineteetraacetic acid (EDTA), a sodium salt thereof,or heparin.

Additional options for use of the invention include any one or more ofthe following:

Use of a coated substrate according to any described embodiment, forexample a vessel such as a sample collection tube, for example a bloodcollection tube and/or a closed-ended sample collection tube; a vial; aconduit; a cuvette; or a vessel part, for example a stopper; or asyringe, or a syringe part, for example a barrel or piston. forreception and/or storage and/or delivery of a compound or composition.

The use of a coated substrate according to any described embodiment iscontemplated for storing insulin.

The use of a coated substrate according to any described embodiment iscontemplated for storing blood. Optionally, the stored blood is viablefor return to the vascular system of a patient.

Use of a coating according to any described embodiment is contemplatedas (i) a lubricity layer having a lower frictional resistance than theuncoated surface; and/or (ii) a hydrophobic layer that is morehydrophobic than the uncoated surface.

Other aspects of the invention include any of the uses defined above inthe summary section.

The following is a more detailed description of the invention. It startswith a general description of the lubricity coating and hydrophobiccoating of present invention, then describes the equipment suitable toprepare the coating of present invention and subsequently describes thecoating embodiments, the coated vessels, and the methods for theirproduction.

IA. Lubricity Coating

Devices designed to deliver parenteral drug products have moveableelastomeric plungers to push the product from the device. Plungers oftenare provided with a lubricious surface to ease movement of the plunger.Free silicon oil is traditionally employed to create a lubricioussurface, but free oil has been implicated in aggregation anddenaturation of proteins.

Silicon oil, a low molecular weight polydimethylsiloxane (PDMS), hasbeen the primary traditional means of making glass and plastic surfaceslubricious and compatible with elastomeric plungers. It is generallysprayed or wiped on the inside of the device. These methods deposit athin liquid layer of silicon oil. Attempts to permanently adhere the oilon the surface of the device through a baking process have improved theadhesion but silicon oil extractables are still found. Non-uniformity ofsilicon oil on devices is problematic and can lead to syringe breakageor misfiring when employed in auto injectors.

Non-uniformity of silicon oil arises from improper or poor applicationof the oil, settling/flow over time under the effects of gravity, andpressure from plungers. During vacuum placement of plungers into thedevice, the plunger will push silicon oil from the top of the devicedown to the final resting location of the plunger, See FIG. 3A. Thesilicon oil between the ribs of the plunger and the glass surface of thedevice will, over time, flow out of the space between the plunger andsyringe wall under the pressure of the plunger. Additionally it has beenfound that silicon oil “settles” or flows under gravity to alter thedistribution of the oil. FIGS. 3A-3C demonstrate examples of silicon oilnon-uniformity.

Non uniformity of silicon oil is responsible for a variety of problems,including localized exposure of drug product to a large depot of oil,high break loose forces, and unsmooth operation of the devices due tovariable glide forces. Variable glide forces and high break loose forcesare particularly problematic with auto injectors, since auto injectorsare designed to work with a known and consistent force.

The lubricity coating of present invention is created from a plasma thatproduces a uniform, firmly attached lubricious coating. It has asuperior performance relative to existing lubricity approaches,comparing wetting tension, plunger force, and extractables andleachables.

The lubricity coating of the invention is deposited using a PECVDprocess that typically utilizes an organosilicon precursor (preferably acyclic organosilicon precursor, in particularoctamethylcyclotetrasiloxane (OMCTS)), oxygen, radiofrequency andcharged electrodes to create the plasma. Without being bound by theory,it is believed that at the pressures and powers that are used, theplasma process is driven by electron impact ionization; that is, theelectrons in the process are the driving force behind the chemistry. Theprocess utilizes radiofrequency to excite electrons, resulting in lowertemperatures than the other standard method of adding energy toelectrons in plasmas, microwaves. The plasma, containing a mixture ofhigh energy electrons and ions of the gases, deposits a coatingcontaining silicon and oxygen and methyl groups attached to the silicon.High energy electrons activate the substrate surface and bonds reformbetween the surface and the silicon/oxygen/methyl species from theOMCTS. A covalently bound uniform, continuous coating is deposited onthe surface.

Since the coating is deposited from plasma, which uniformly fills thecontainer it occupies, at a molecular level, a uniform composition coatis believed to be achieved. The lubricity coating is essentiallycomprised of silicon, oxygen and methyl groups. AFM, FTIR, TOF/SIMS, XPSand scanning electron microscopy confirm the purity and uniformity.

TABLE I Lubricity Coating on Syringes Wetting Tension Standard PackageType (dyne/cm) Deviation Cyclic Olefin Syringe with CV Holdings 36 0.57SiOxCyHz Lubricity Coating Borosilicate Glass Syringe with 37 0.57Silicone Oil Cyclic Olefin Container with Triboglide <30 N/A Coating

Precision of the wetting tension measurement is +/−3 dyne/cm

Table I, above, shows the wetting tension measured a COC syringe withSiOxCyHz lubricity coating, a borosilicate glass syringe coated withsilicon oil (Dow Corning Medical Grade 360), and a COC container withTriboglide Coating (another known liquid lubricant). A wetting tensionof 30 dyne/cm is considered very hydrophobic, a wetting tension of 70dyne/cm very hydrophilic. All three surfaces therefore show appreciablehydrophobicity. The lubricity coating of the invention shows ahydrophobicity similar to silicon oil, but less than Triboglide.

The lubricity coating of present invention can also be applied onto aSiO_(x) barrier coating. This is shown in FIG. 21, which contains a TEMpicture of a lubricity coating on a SiO₂ layer,

The determination of an extractables profile for an exemplary lubricitycoating is described in Example Z. The lubricity coating preferablyprovides less extractables than a silicon oil coated glass syringe(Example Z), typically less than 10% of the extractables of the latter.In general, the lubricity coating extractables amount ranges from 1 to500 μg/L, preferably from 5 to 300 μg/L. Typically, it may range from 80to 300 μg/L, based on the static method of determination.

Since the lubricity coating is attached to the coated surface, thecoating will remain uniform over time and consistent, reproducible breakloose and glide forces will be maintained. Exemplary break loose andglide forces are shown in Table II:

TABLE II Plunger Force Comparison of Lubricity Coatings InitiationMaintenance Package Type Force (N) Force (N) Uncoated Cydic OlefinSyringe >15 >15 Cydic Olefin Syringe with CV Holdings 4.1 3.5 SiOCHLubricity Coating Cydic Olefin Syringe with Silicone Oil 8.2 6.3 CydicOlefin Cotainer with Triboglide 5.7 2.0 Coating

The lubricity coating optionally provides a consistent plunger forcethat reduces the difference between the break loose force (Fi) and theglide force (Fm). These two forces are important performance measuresfor the effectiveness of a lubricity coating. For Fi and Fm, it isdesired to have a low, but not too low value. With too low Fi, whichmeans a too low level of resistance (the extreme being zero),premature/unintended flow may occur, which might e.g. lead to anunintentional premature or uncontrolled discharge of the content of aprefilled syringe.

In order to achieve a sufficient lubricity (e.g. to ensure that asyringe plunger can be moved in the syringe, but to avoid uncontrolledmovement of the plunger), the following ranges of Fi and Fm should beadvantageously maintained: Fi: 2.5 to 5 lbs, preferably 2.7 to 4.9 lbs,and in particular 2.9 to 4.7 lbs; Fm: 2.5 to 8.0 lbs, preferably 3.3 to7.6 lbs, and in particular 3.3 to 4 lbs. Further advantageous Fi and Fmvalues can be found in the Tables of the Examples. From the Examples, itcan also be seen that lower Fi and Fm values can be achieved than theranges indicated above. Coatings having such lower values are alsoconsidered to be encompassed by the present invention.

Table II compares a lubricity coating according to the invention on asyringe with silicon oil and Triboglide lubricity coatings. The resultsdemonstrate that the lubricity coating preferably provides superiorconsistency between Fi and Fm.

Break-loose and glide forces are important throughout a device's shelflife especially in automated devices such as auto-injectors. Changes inbreak-loose and/or glide forces can lead to misfiring of auto injectors.

The present lubricity coatings can optionally have more than 10-timesless silicon extractables compared to a silicon oil coated syringe.During the PECVD process, the lubricity coating is bonded to thesyringe. This results in dramatically lower extractables. Throughprocess optimization, the total silicon extractables from the lubricitycoating can be further reduced.

The lubricity coating according to present invention is typicallyprepared by PECVD using an organosilicon precursor and O2. In aparticular embodiment, these two precursors are mixed with a carriergas, typically a noble gas, and most typically Argon.

The organosilicon precursor may be any of the precursors listedelsewhere in present description. However, cyclic organosiliconprecursors, in particular monocyclic organosilicon precursors (like themonocyclic precursors listed elsewhere in present description), andspecifically OMCTS, are particularly suitable to achieve a lubriciouscoating.

The presence of O2 and/or of a carrier gas, in particular of Argon, canincrease the lubricity of the resulting coating. The presence of both O2and Ar together with the organosilicon precursor is particularlyadvantageous. Generally, in order to get a lubricity coating, O2 ispresent in an amount (which can, e.g. be expressed by the flow rate insccm) which is does not very much exceed the organosilicon amount andpreferably is lower than the organosilicon amount. In contrast, in orderto achieve a barrier coating, the amount of O2 typically is at least oneorder of magnitude higher than the amount of organosilicon precursor. Inparticular, the volume ratio (in sccm) of O2 to organosilicon precursorfor a lubricity coating is from 0:1 to 1:1, even optionally from 0:1 to0.5:1 or even from 0:1 to 0.1:1. It is preferred that some O2 ispresent, optionally in an amount of from 0.01:1 to 0.5:1, evenoptionally from 0.05:1 to 0.4:1, in particular from 0.1:1 to 0.2:1 inrelation to the organosilicon precursor. The presence of O2 in a volumeof about 5% to about 35% (v/v in sccm) in relation to the organosiliconprecursor, in particular of about 10% to about 20% and in a ratio asgiven in the Examples is specifically suitable to achieve a lubricitycoating.

In one aspect of the invention, a carrier gas is absent in the reactionmixture, in another aspect of the invention, it is present. In aparticular aspect of the invention, the carrier gas is present and it isArgon. When Ar is the carrier gas and it is present in the reactionmixture, it is typically present in a volume (in sccm) exceeding thevolume of the organosilicon precursor (and the volume of O₂, ifpresent).

Typically, the plasma in the PECVD process is generated at RF frequency.The plasma is typically generated with an electric power of from 0.1 to25 W, optionally from 1 to 22 W, optionally from 1 to 10 W, evenoptionally from 1 to 5 W, optionally from 2 to 4 W, for example of 3 W,optionally from 3 to 17 W, even optionally from 5 to 14 W, for example 6or 7.5 W, optionally from 7 to 11 W, for example of 8 W. The ratio ofthe electrode power to the plasma volume can be less than 10 W/ml,optionally is from 5 W/ml to 0.1 W/ml, optionally is from 6 W/ml to 0.1W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally from 2 W/ml to0.2 W/ml. Low power levels are believed by the inventors to be mostadvantageous (e.g. power levels of from 2 to 3.5 W and the power levelsgiven in the Examples) to prepare a lubricity coating. These powerlevels are suitable for applying lubricity coatings to syringes andsample tubes and vessels of similar geometry having a void volume of 1to 3 mL in which PECVD plasma is generated. It is contemplated that forlarger or smaller objects the power applied should be increased orreduced accordingly to scale the process to the size of the substrate.

The substrate of the lubricity coating is typically a surface made ofplastic (e.g. the interior surface of a plastic syringe). Typicalplastic substrates are listed elsewhere in present description.Particularly suitable substrates in the context of present invention areCOC, PET, and polypropylene, with COC being specifically suitable.

In one specific aspect of present invention, the substrate is a plasticwhich is already coated with a coating, e.g. a SiOx barrier coating. Onsaid existing coating, the lubricity coating is applied. Vice versa, thelubricity coating can also be coated with another coating, e.g. abarrier coating.

In a very particular aspect of the present invention, the lubricity isinfluenced by the roughness of the lubricity coating. It hassurprisingly been found that a rough surface of the coating iscorrelated with enhanced lubricity. The roughness of the lubricitycoating is increased with decreasing power (in Watts) energizing theplasma, and by the presence of O2 in the amounts described above.

The vessels (e.g. syringe barrels and/or plungers) coated with alubricity coating according to present invention have a higher lubricity(determined, e.g. by measuring the Fi and/or Fm) than the uncoatedvessels. They also have a higher lubricity than vessels coated with aSiOx coating as described herein.

Exemplary reaction conditions for preparing a lubricity coatingaccording to the present invention in a 3 ml sample size syringe with a⅛″ diameter tube (open at the end) are as follows:

-   Flow rate ranges:-   OMCTS: 0.5-5.0 sccm-   Oxygen: 0.1-5.0 sccm-   Argon: 1.0-20 sccm-   Power: 0.1-10 watts-   Specific Flow rates:-   OMCTS: 2.0 sccm-   Oxygen: 0.7 sccm-   Argon: 7.0 sccm-   Power: 3.5 watts

The coating apparatus can advantageously include heated delivery linesfrom the exit of the OMCTS reservoir to as close as possible to the gasinlet into the syringe.

The lubricity coating is described in more detail under V.C below.

IB. Hydrophobic Coating

Silicon, like carbon, is tetravalent, thus preferring to form fourbonds. In glass, silicon bonds to oxygen, which is bonded to anothersilicon (siloxane bonds, Si—O—Si), resulting in a SiO₂ polymer. Anetwork of siloxane bonds form, creating silica. At the surface ofsilica, oxygen atoms that are not bonded to other silicon atoms exist ashydroxyl (OH) groups, known as silanols. Terminal groups at a glasssurface can thus be silanols with one or more OH groups, or siloxanebonds. Lone silanols are found in crystalline silica surfaces such asthe SiO_(x) coating described herein. Both lone and vicinal silanols arefound in amorphous silicas such as traditional glasses. Without beingbound by theory, the chemical nature of the surface chemistry isbelieved to be largely determined by the density of silanol groups onit. A fully hydroxylated glass surface, that has the maximum density ofsilanols possible, is quite hydrophilic. A surface on which the silanolsare condensed to form siloxane bonds, (i.e., minimal density ofsilanols) has a hydrophobic nature. Using the coating technologies asdescribed herein, it is possible to control the density of silanols onthe surface of the coating. The chemistry of the plasma deposition canbe controlled to create either a fully hydroxylated, hydrophilic surfaceor a minimally hydroxylated, hydrophobic surface.

Table III, below, shows the wetting tension of four different drugcontainer surfaces. A wetting tension of 20 dyne/cm is considered veryhydrophobic, while a wetting tension of 80 dyne/cm is very hydrophilic.The data in Table III shows the SiO₂ barrier coating is as hydrophilicas traditional glass. In contrast, the lubricity coating of presentinvention (designated as SiOxCyHz Coating in the table) has ahydrophobic nature similar to that of COC.

TABLE III Content Contact Surfaces Wetting Tension Package Type(dyne/cm) Cyclic Olefin Container with SiO₂ Coating >70 BorosilicateGlass Container >70 Cyclic Olefin Container with SiOxCyHz Coating 46Uncoated Cyclic Olefin Container 36

Precision of the wetting tension measurement was +/−3 dyne/cm

“Hydrophobic” in the context of present invention may mean morehydrophobic than the uncoated substrate (may it be plastic or anothercoating). However, as is demonstrated in FIG. 23, it can also mean thatthe surface is as hydrophobic as a comparative hydrophobic surface (likethe COC surface in FIG. 23d ). Preferably, “hydrophobic” means a wettingtension of less than 60 dyne/cm, more preferably less than 50 dyne/cm,in particular a wetting tension of from 15 dyne/cm to 46 dyne/cm or from20 dyne/cm to 35 dyne/cm.

The PECVD conditions for a hydrophobic surface coating are contemplatedto be similar to those for a lubricity coating, and in fact it ispossible that one coating can provide both functions to a useful degree.

The difference in conditions to apply a hydrophobic coating to an SiOxcoating is illustrated by comparing a SiOx coating protocol(US2010/0298738 A1, par. 1000 to 1011) with a hydrophobic coatingprotocol (US2010/0298738 A1, par. 1012 to 1023). The equipment and theprecursor (HMDSO) are the same in these two protocols, but theconditions are different, and generally milder for the hydrophobiccoating, as illustrated by the exemplary conditions below:

Parameter SiO_(x) Protocol Hydrophobic Protocol O₂ flow rate 90 sccm 60sccm Pressure within tube 300 mTorr 270 mTorr during gas delivery PECVDRF Power 50 Watts 39 Watts Power on time 5 sec 7 sec

An advantageous feature of the hydrophobic coating is that it optionallycan be applied using the same equipment as the SiOx coating and/or thelubricity coating, so all PECVD coatings can be applied sequentially ina single process, with minor changes in conditions.

The hydrophobic coating can have a lower wetting tension than theuncoated surface, optionally a wetting tension of from 20 to 72 dyne/cm,optionally from 30 to 60 dyne/cm, optionally from 30 to 50 dyne/cm, 30to 40 dyne/cm, optionally 34 dyne/cm. One proposed wetting tension,namely 34 dyne/cm, is similar to that of a fluid silicone coating onborosilicate glass (30 dynes/cm).

FIG. 23 shows the effect of a hydrophobic coating according to presentinvention and of a hydrophilic coating according to present invention.

II. Vessel Holders

II.A. For producing the coating of present invention, a vessel holder isprovided. The portable vessel holders 38, 50, and 482 are provided forholding and conveying a vessel having an opening while the vessel isprocessed. The vessel holder includes a vessel port, a second port, aduct, and a conveyable housing.

II.A. The vessel port is configured to seat a vessel opening in amutually communicating relation. The second port is configured toreceive an outside gas supply or vent. The duct is configured forpassing one or more gases between a vessel opening seated on the vesselport and the second port. The vessel port, second port, and duct areattached in substantially rigid relation to the conveyable housing.Optionally, the portable vessel holder weighs less than five pounds. Anadvantage of a lightweight vessel holder is that it can more readily betransported from one processing station to another.

II.A. In certain embodiments of the vessel holder the duct morespecifically is a vacuum duct and the second port more specifically is avacuum port. The vacuum duct is configured for withdrawing a gas via thevessel port from a vessel seated on the vessel port. The vacuum port isconfigured for communicating between the vacuum duct and an outsidesource of vacuum. The vessel port, vacuum duct, and vacuum port can beattached in substantially rigid relation to the conveyable housing.

II.A. The vessel holders are shown, for example, in FIG. 1. The vesselholder 50 has a vessel port 82 configured to receive and seat theopening of a vessel 80. The interior surface of a seated vessel 80 canbe processed via the vessel port 82. The vessel holder 50 can include aduct, for example a vacuum duct 94, for withdrawing a gas from a vessel80 seated on the vessel port 92. The vessel holder can include a secondport, for example a vacuum port 96 communicating between the vacuum duct94 and an outside source of vacuum, such as the vacuum pump 98. Thevessel port 92 and vacuum port 96 can have sealing elements, for exampleO-ring butt seals, respectively 100 and 102, or side seals between aninner or outer cylindrical wall of the vessel port 82 and an inner orouter cylindrical wall of the vessel 80 to receive and form a seal withthe vessel 80 or outside source of vacuum 98 while allowingcommunication through the port. Gaskets or other sealing arrangementscan or also be used.

II.A. The vessel holder such as 50 can be made of any material, forexample thermoplastic material and/or electrically nonconductivematerial. Or, the vessel holder such as 50 can be made partially, oreven primarily, of electrically conductive material and faced withelectrically nonconductive material, for example in the passages definedby the vessel port 92, vacuum duct 94, and vacuum port 96. Examples ofsuitable materials for the vessel holder 50 are: a polyacetal, forexample Delrin® acetal material sold by E. I. du Pont De Nemours andCompany, Wilmington Delaware; polytetrafluoroethylene (PTFE), forexample Teflon® PTFE sold by E. I. du Pont De Nemours and Company,Wilmington Delaware; Ultra-High-Molecular-Weight Polyethylene (UHMWPE);High density Polyethylene (HDPE); or other materials known in the art ornewly discovered.

II.A. FIG. 1 also illustrates that the vessel holder, for example 50,can have a collar 116 for centering the vessel 80 when it is approachingor seated on the port 92.

FIG. 10 is an alternative construction for a vessel holder 482 usable,for example, with the embodiments of any other Figure. The vessel holder482 comprises an upper portion 484 and a base 486 joined together at ajoint 488. A sealing element, for example an O-ring 490 (the right sideof which is cut away to allow the pocket retaining it to be described)is captured between the upper portion 484 and the base 486 at the joint488. In the illustrated embodiment, the O-ring 490 is received in anannular pocket 492 to locate the O-ring when the upper portion 484 isjoined to the base 486.

II.B. In this embodiment, the O-ring 490 is captured and bears against aradially extending abutment surface 494 and the radially extending wall496 partially defining the pocket 492 when the upper portion 484 and thebase 486 are joined, in this case by the screws 498 and 500. The O-ring490 thus seats between the upper portion 484 and base 486. The O-ring490 captured between the upper portion 484 and the base 486 alsoreceives the vessel 80 (removed in this figure for clarity ofillustration of other features) and forms a first O-ring seal of thevessel port 502 about the vessel 80 opening, analogous to the O-ringseal arrangement about the vessel back opening.

II.B. In this embodiment, though not a requirement, the vessel port 502has both the first O-ring 490 seal and a second axially spaced O-ring504 seal, each having an inner diameter such as 506 sized to receive theouter diameter (analogous to the sidewall) of a vessel such as 80 forsealing between the vessel port 502 and a vessel such as 80. The spacingbetween the O-rings 490 and 504 provides support for a vessel such as 80at two axially spaced points, preventing the vessel such as 80 frombeing skewed with respect to the O-rings 490 and 504 or the vessel port502. In this embodiment, though not a requirement, the radiallyextending abutment surface 494 is located proximal of the O-ring 490 and506 seals and surrounding the vacuum duct 508.

III. Processing Vessels Seated on Vessel Holders

III.A. FIG. 1 shows a method for processing a vessel 80. The method canbe carried out as follows.

III.A. A vessel 80 can be provided having an opening 82 and a wall 86defining an interior surface 88. As one embodiment, the vessel 80 can beformed in and then removed from a mold such as 22. Optionally within 60seconds, or within 30 seconds, or within 25 seconds, or within 20seconds, or within 15 seconds, or within 10 seconds, or within 5seconds, or within 3 seconds, or within 1 second after removing thevessel from the mold, or as soon as the vessel 80 can be moved withoutdistorting it during processing (assuming that it is made at an elevatedtemperature, from which it progressively cools), the vessel opening 82can be seated on the vessel port 92. Quickly moving the vessel 80 fromthe mold 22 to the vessel port 92 reduces the dust or other impuritiesthat can reach the surface 88 and occlude or prevent adhesion of thebarrier or other type of coating 90. Also, the sooner a vacuum is drawnon the vessel 80 after it is made, the less chance any particulateimpurities have of adhering to the interior surface 88.

III.A. A vessel holder such as 50 comprising a vessel port 92 can beprovided. The opening 82 of the vessel 80 can be seated on the vesselport 92. Before, during, or after seating the opening 82 of the vessel80 on the vessel port 92, the vessel holder such as 40 can betransported into engagement with one or more of the bearing surfaces220-240 to position the vessel holder 40 with respect to the processingdevice or station such as 24.

III.A. The interior surface 88 of the seated vessel 80 can be thenprocessed via the vessel port 92 at the first processing station, whichcan be, as one example, the barrier application or other type of coatingstation 28 shown in FIG. 1. The vessel holder 50 and seated vessel 80are transported from the first processing station 28 to the secondprocessing station, for example the processing station 32. The interiorsurface 88 of the seated vessel 80 can be processed via the vessel port92 at the second processing station such as 32.

III.A. Any of the above methods can include the further step of removingthe vessel 80 from the vessel holder such as 66 following processing theinterior surface 88 of the seated vessel 80 at the second processingstation or device.

III.A. Any of the above methods can include the further step, after theremoving step, of providing a second vessel 80 having an opening 82 anda wall 86 defining an interior surface 88. The opening 82 of the secondvessel such as 80 can be seated on the vessel port 92 of another vesselholder such as 38. The interior surface of the seated second vessel 80can be processed via the vessel port 92 at the first processing stationor device such as 24. The vessel holder such as 38 and seated secondvessel 80 can be transported from the first processing station or device24 to the second processing station or device such as 26. The seatedsecond vessel 80 can be processed via the vessel port 92 by the secondprocessing station or device 26.

IV. PECVD Apparatus for Making Vessels

IV.A. PECVD Apparatus Including Vessel Holder, Internal Electrode,Vessel as Reaction Chamber

IV.A. A PECVD apparatus suitable for performing the present inventionincludes a vessel holder, an inner electrode, an outer electrode, and apower supply. A vessel seated on the vessel holder defines a plasmareaction chamber, which optionally can be a vacuum chamber. Optionally,a source of vacuum, a reactant gas source, a gas feed or a combinationof two or more of these can be supplied. Optionally, a gas drain, notnecessarily including a source of vacuum, is provided to transfer gas toor from the interior of a vessel seated on the port to define a closedchamber.

IV.A. The PECVD apparatus can be used for atmospheric-pressure PECVD, inwhich case the plasma reaction chamber does not need to function as avacuum chamber.

IV.A. In FIG. 1, the vessel holder 50 comprises a gas inlet port 104 forconveying a gas into a vessel seated on the vessel port. The gas inletport 104 has a sliding seal provided by at least one O-ring 106, or twoO-rings in series, or three O-rings in series, which can seat against acylindrical probe 108 when the probe 108 is inserted through the gasinlet port 104. The probe 108 can be a gas inlet conduit that extends toa gas delivery port at its distal end 110. The distal end 110 of theillustrated embodiment can be inserted deep into the vessel 80 forproviding one or more PECVD reactants and other gaseous reactant orprocess gases.

IV.A. FIG. 11 shows additional optional details of the coating station28 that are usable, for example, with all the illustrated embodiments.The coating station 28 can also have a main vacuum valve 574 in itsvacuum line 576 leading to the pressure sensor 152. A manual bypassvalve 578 is provided in the bypass line 580. A vent valve 582 controlsflow at the vent 404.

IV.A. Flow out of the PECVD gas or precursor source 144 is controlled bya main reactant gas valve 584 regulating flow through the main reactantfeed line 586. One component of the gas source 144 is the organosiliconliquid reservoir 588. The contents of the reservoir 588 are drawnthrough the organosilicon capillary line 590, which is provided at asuitable length to provide the desired flow rate. Flow of organosiliconvapor is controlled by the organosilicon shut-off valve 592. Pressure isapplied to the headspace 614 of the liquid reservoir 588, for example apressure in the range of 0-15 psi (0 to 78 cm. Hg), from a pressuresource 616 such as pressurized air connected to the headspace 614 by apressure line 618 to establish repeatable organosilicon liquid deliverythat is not dependent on atmospheric pressure (and the fluctuationstherein). The reservoir 588 is sealed and the capillary connection 620is at the bottom of the reservoir 588 to ensure that only neatorganosilicon liquid (not the pressurized gas from the headspace 614)flows through the capillary tube 590. The organosilicon liquidoptionally can be heated above ambient temperature, if necessary ordesirable to cause the organosilicon liquid to evaporate, forming anorganosilicon vapor. Oxygen is provided from the oxygen tank 594 via anoxygen feed line 596 controlled by a mass flow controller 598 andprovided with an oxygen shut-off valve 600.

IV.A. Referring especially to FIG. 1, the processing station 28 caninclude an electrode 160 fed by a radio frequency power supply 162 forproviding an electric field for generating plasma within the vessel 80during processing. In this embodiment, the probe 108 is alsoelectrically conductive and is grounded, thus providing acounter-electrode within the vessel 80. Alternatively, in any embodimentthe outer electrode 160 can be grounded and the probe 108 directlyconnected to the power supply 162.

IV.A. In the embodiment of FIG. 1, the outer electrode 160 can either begenerally cylindrical as illustrated in FIGS. 1 and 2 or a generallyU-shaped elongated channel as illustrated in FIG. 1 (FIG. 2 being anembodiment of the section taken along section line A-A of FIG. 1). Eachillustrated embodiment has one or more sidewalls, such as 164 and 166,and optionally a top end 168, disposed about the vessel 80 in closeproximity.

IV.A The electrode 160 shown in FIG. 1 can be shaped like a “U” channelwith its length into the page and the puck or vessel holder 50 can movethrough the activated (powered) electrode during the treatment/coatingprocess. Note that since external and internal electrodes are used, thisapparatus can employ a frequency between 50 Hz and 1 GHz applied from apower supply 162 to the U channel electrode 160. The probe 108 can begrounded to complete the electrical circuit, allowing current to flowthrough the low-pressure gas(es) inside of the vessel 80. The currentcreates plasma to allow the selective treatment and/or coating of theinterior surface 88 of the device.

IV.A The electrode in FIG. 1 can also be powered by a pulsed powersupply. Pulsing allows for depletion of reactive gases and then removalof by-products prior to activation and depletion (again) of the reactivegases. Pulsed power systems are typically characterized by their dutycycle which determines the amount of time that the electric field (andtherefore the plasma) is present. The power-on time is relative to thepower-off time. For example a duty cycle of 10% can correspond to apower on time of 10% of a cycle where the power was off for 90% of thetime. As a specific example, the power might be on for 0.1 second andoff for 1 second. Pulsed power systems reduce the effective power inputfor a given power supply 162, since the off-time results in increasedprocessing time. When the system is pulsed, the resulting coating can bevery pure (no by products or contaminants). Another result of pulsedsystems is the possibility to achieve atomic layer or coating deposition(ALD). In this case, the duty cycle can be adjusted so that the power-ontime results in the deposition of a single layer or coating of a desiredmaterial. In this manner, a single atomic layer or coating iscontemplated to be deposited in each cycle. This approach can result inhighly pure and highly structured coatings (although at the temperaturesrequired for deposition on polymeric surfaces, temperatures optionallyare kept low (<100° C.) and the low-temperature coatings can beamorphous).

IV.A. An alternative coating station employs a microwave cavity insteadof an outer electrode. The energy applied can be a microwave frequency,for example 2.45 GHz. However, in the context of present invention, aradiofrequency is preferred.

V.1 PRecursors for PECVD Coating

The precursor for the PECVD coating of the present invention is broadlydefined as an organometallic precursor. An organometallic precursor isdefined in this specification as comprehending compounds of metalelements from Group III and/or Group IV of the Periodic Table havingorganic residues, e.g. hydrocarbon, aminocarbon or oxycarbon residues.Organometallic compounds as presently defined include any precursorhaving organic moieties bonded to silicon or other Group III/IV metalatoms directly, or optionally bonded through oxygen or nitrogen atoms.The relevant elements of Group III of the Periodic Table are Boron,Aluminum, Gallium, Indium, Thallium, Scandium, Yttrium, and Lanthanum,Aluminum and Boron being preferred. The relevant elements of Group IV ofthe Periodic Table are Silicon, Germanium, Tin, Lead, Titanium,Zirconium, Hafnium, and Thorium, with Silicon and Tin being preferred.Other volatile organic compounds can also be contemplated. However,organosilicon compounds are preferred for performing present invention.

An organosilicon precursor is contemplated, where an “organosiliconprecursor” is defined throughout this specification most broadly as acompound having at least one of the linkages:

The first structure immediately above is a tetravalent silicon atomconnected to an oxygen atom and an organic carbon atom (an organiccarbon atom being a carbon atom bonded to at least one hydrogen atom).The second structure immediately above is a tetravalent silicon atomconnected to an —NH— linkage and an organic carbon atom (an organiccarbon atom being a carbon atom bonded to at least one hydrogen atom).Optionally, the organosilicon precursor is selected from the groupconsisting of a linear siloxane, a monocyclic siloxane, a polycyclicsiloxane, a polysilsesquioxane, a linear silazane, a monocyclicsilazane, a polycyclic silazane, a polysilsesquiazane, and a combinationof any two or more of these precursors. Also contemplated as aprecursor, though not within the two formulas immediately above, is analkyl trimethoxysilane. If an oxygen-containing precursor (e.g. asiloxane) is used, a representative predicted empirical compositionresulting from PECVD under conditions forming a hydrophobic orlubricating coating would be Si_(w)O_(x)C_(y)H_(z) as defined in theDefinition Section, while a representative predicted empiricalcomposition resulting from PECVD under conditions forming a barriercoating would be SiO_(x), where x in this formula is from about 1.5 toabout 2.9. If a nitrogen-containing precursor (e.g. a silazane) is used,the predicted composition would be Si_(w*)N_(x*)C_(y*)H_(z*), i.e. inSi_(w)O_(x)C_(y)H_(z) as specified in the Definition Section, O isreplaced by N and the indices are adapted to the higher valency of N ascompared to O (3 instead of 2). The latter adaptation will generallyfollow the ratio of w, x, y and z in a siloxane to the correspondingindices in its aza counterpart. In a particular aspect of the invention,Si_(w*)N_(x*)C_(y*)H_(z*) in which w*, x*, y*, and z* are defined thesame as w, x, y, and z for the siloxane counterparts, but for anoptional deviation in the number of hydrogen atoms.

One type of precursor starting material having the above empiricalformula is a linear siloxane, for example a material having thefollowing formula:

in which each R is independently selected from alkyl, for examplemethyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl,alkyne, or others, and n is 1, 2, 3, 4, or greater, optionally two orgreater. Several examples of contemplated linear siloxanes are

hexamethyldisiloxane (HMDSO),

-   -   octamethyltrisiloxane,    -   decamethyltetrasiloxane,    -   dodecamethylpentasiloxane,        or combinations of two or more of these. The analogous silazanes        in which —NH— is substituted for the oxygen atom in the above        structure are also useful for making analogous coatings. Several        examples of contemplated linear silazanes are        octamethyltrisilazane, decamethyltetrasilazane, or combinations        of two or more of these.

V.C. Another type of precursor starting material is a monocyclicsiloxane, for example a material having the following structuralformula:

in which R is defined as for the linear structure and “a” is from 3 toabout 10, or the analogous monocyclic silazanes. Several examples ofcontemplated hetero-substituted and unsubstituted monocyclic siloxanesand silazanes include

-   -   1,3,5-trimethyl-1,3,5-tris(3,3,3-trifluoropropyl)methyl]cyclotrisiloxane    -   2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane,    -   pentamethylcyclopentasiloxane,    -   pentavinylpentamethylcyclopentasiloxane,    -   hexamethylcyclotrisiloxane,    -   hexaphenylcyclotrisiloxane,    -   octamethylcyclotetrasiloxane (OMCTS),    -   octaphenylcyclotetrasiloxane,    -   decamethylcyclopentasiloxane    -   dodecamethylcyclohexasiloxane,    -   methyl(3,3,3-trifluoropropl)cyclosiloxane,    -   Cyclic organosilazanes are also contemplated, such as    -   Octamethylcyclotetrasilazane,    -   1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasilazane        hexamethylcyclotrisilazane,    -   octamethylcyclotetrasilazane,    -   decamethylcyclopentasilazane,    -   dodecamethylcyclohexasilazane, or        combinations of any two or more of these.

V.C. Another type of precursor starting material is a polycyclicsiloxane, for example a material having one of the following structuralformulas:

in which Y can be oxygen or nitrogen, E is silicon, and Z is a hydrogenatom or an organic substituent, for example alkyl such as methyl, ethyl,propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl, alkyne, or others.When each Y is oxygen, the respective structures, from left to right,are a silatrane, a silquasilatrane, and a silproatrane. When Y isnitrogen, the respective structures are an azasilatrane, anazasilquasiatrane, and an azasilproatrane.

V.C. Another type of polycyclic siloxane precursor starting material isa polysilsesquioxane, with the empirical formula RSiO_(1.5) and thestructural formula:

in which each R is a hydrogen atom or an organic substituent, forexample alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl,t-butyl, vinyl, alkyne, or others. Two commercial materials of this sortare SST-eM01 poly(methylsilsesquioxane), in which each R is methyl, andSST-3MH1.1 poly(Methyl-Hydridosilsesquioxane), in which 90% of the Rgroups are methyl, 10% are hydrogen atoms. This material is available ina 10% solution in tetrahydrofuran, for example. Combinations of two ormore of these are also contemplated. Other examples of a contemplatedprecursor are methylsilatrane, CAS No. 2288-13-3, in which each Y isoxygen and Z is methyl, methylazasilatrane, poly(methylsilsesquioxane)(e.g. SST-eM01 poly(methylsilsesquioxane)), in which each R optionallycan be methyl, SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane) (e.g.SST-3MH1.1 poly(Methyl-Hydridosilsesquioxane)), in which 90% of the Rgroups are methyl and 10% are hydrogen atoms, or a combination of anytwo or more of these.

V.C. The analogous polysilsesquiazanes in which —NH— is substituted forthe oxygen atom in the above structure are also useful for makinganalogous coatings. Examples of contemplated polysilsesquiazanes are apoly(methylsilsesquiazane), in which each R is methyl, and apoly(Methyl-Hydridosilsesquiazane, in which 90% of the R groups aremethyl, 10% are hydrogen atoms. Combinations of two or more of these arealso contemplated.

V.C. One particularly contemplated precursor for the lubricity layer orcoating according to the present invention is a monocyclic siloxane, forexample is octamethylcyclotetrasiloxane.

One particularly contemplated precursor for the hydrophobic layer orcoating according to the present invention is a monocyclic siloxane, forexample is octamethylcyclotetrasiloxane. Another particularlycontemplated precursor for the hydrophobic layer or coating according tothe present invention is a linear siloxane, for example HMDSO.

One particularly contemplated precursor for the barrier coatingaccording to the present invention is a linear siloxane, for example isHMDSO.

V.C. In any of the coating methods according to the present invention,the applying step optionally can be carried out by vaporizing theprecursor and providing it in the vicinity of the substrate. E.g., OMCTSis usually vaporized by heating it to about 50° C. before applying it tothe PECVD apparatus.

V.2 General PECVD Method

In the context of the present invention, the following PECVD method isgenerally applied, which contains the following steps:

(a) providing a process gas comprising a precursor as defined herein,optionally an oxidizing gas, optionally a carrier gas, and optionally ahydrocarbon; and

(b) generating a plasma from the process gas, thus forming a coating onthe substrate surface by plasma enhanced chemical vapor deposition(PECVD).

The plasma coating technology used herein is based on Plasma EnhancedChemical Vapor Deposition (PECVD). Methods and apparatus suitable toperform said PECVD coatings are described in EP10162755.2 filed May 12,2010; EP10162760.2 filed May 12, 2010; EP10162756.0 filed May 12, 2010;EP10162758.6 filed May 12, 2010; EP10162761.0 filed May 12, 2010; andEP10162757.8 filed May 12, 2010. The PECVD methods and apparatus asdescribed therein are suitable to perform the present invention and aretherefore incorporated herein by reference.

Without being bound by theory, it is assumed that the coating iscovalently attached to the coated surface (may it be the plasticsubstrate surface or the surface of a coating which is already presenton the substrate surface, e.g. a SiO_(x) barrier coating) in the PECVDprocess of the invention. The process uses a silicon source (e.g. HMDSOor OMCTS), oxygen, radiofrequency (RF) and charged electrodes to createthe plasma. Optionally, a carrier gas like Argon is present as well. Ahydrocarbon gas may also be present in specific applications. At thepressures and powers that are used, the plasma process is driven byelectron impact ionization; that is, the electrons in the process arethe driving force of the reaction. The process utilizes RF to excite theelectrons, resulting in lower temperatures than traditional standardmethods of energizing electrons in plasmas, i.e., microwaves.

The plasma, which contains a mixture of high energy electrons and ionsof the gases, deposits a silicon and oxide containing coating onto theplastic (e.g. COC) surface. Electrons from the plasma interact at thepolymer surface upon initiation of the plasma reaction, “etching” thesurface by breaking C—H bonds (a similar “etching by breaking bonds”takes place when a coating is coated again, e.g. when a lubricitycoating is applied on a SiOx barrier coating). Under the rightconditions, these sites then are believed to act as nucleation pointswhere the Si—O—Si backbone (which is formed from the ionization of thesilicon containing molecule in the gas phase) bonds with the polymer,from which the coating grows, eventually forming a uniform, continuouscoating over the entire polymer surface. The silicon-carbon (silicon tomethyl groups) bonds in the organosilicon precursor can react withoxygen, breaking the bond between the methyl group and silicon andreforming bonds with the plastic surface or other Si—O groups already onthe surface.

Since the coating is grown from a plasma, which is an ionized gas,completely filling the container it occupies, a dense, uniform andconformal coating is achieved at a molecular level. See FIGS. 21 and 22.The purity of the coating is assured through the use of pure precursorgases. This process results in a surface with uniform, controllableenergy. Analytical characterization of a coating with atomic forcemicroscopy (AFM), FTIR, TOF-SIMS, XPS, electron spectroscopy forchemical analysis (ESCA) and scanning electron microscopy can confirmthe purity and uniformity.

An exemplary preferred embodiment of the PECVD technology will bedescribed in the following sections.

The process utilizes a silicon containing vapor that can be combinedwith oxygen at reduced pressures (mTorr range—atmospheric pressure is760 Torr) inside a container.

An electrical field generated at, e.g., 13.56 MHz [radio frequencyrange] is then applied between an external electrode and an internalgrounded gas inlet to create a plasma. At the pressures and powers thatare used to coat a container, the plasma process is driven by electronimpact ionization, which means the electrons in the process are thedriving force behind the chemistry. Specifically, the plasma drives thechemical reaction through electron impact ionization of the siliconcontaining material [e.g., hexamethyldisiloxane (HMDSO) or otherreactants like octamethylcyclotretrasiloxane (OMCTS)] resulting in asilicon dioxide or Si_(w)O_(x)C_(y)H_(z) coating deposited onto theinterior surfaces of the container. These coatings are in a typicalembodiment on the order of 20 or more nanometers in thickness. HMDSOconsists of an Si—O—Si backbone with six (6) methyl groups attached tothe silicon atoms. The process breaks the Si—C bonds and (at the surfaceof the tube or syringe) reacts with oxygen to create silicon dioxide.Since the coating is grown on an atomic basis, dense, conformal coatingswith thicknesses of 20-30 nanometers can achieve significant barrierproperties. The silicon oxide acts as a physical barrier to gases,moisture, and small organic molecules, and is of greater purity thancommercial glasses. OMCTS results in coatings with lubricity oranti-adhesion properties. Their average thickness is generally higherthan the thickness of the SiO_(x) barrier coating, e.g. from 30 to 1000nm on average. A certain roughness may enhance the lubricious propertiesof the lubricity coating, thus its thickness is advantageously notuniform throughout the coating (see below). However, a uniform lubricitycoating is also considered.

The technology is unique in several aspects:

(a) The process utilizes the rigid container as the vacuum chamber.PECVD conventionally uses a secondary vacuum vessel into which thepart(s) are loaded and coated. Utilizing the container as a vacuumchamber significantly simplifies the process apparatus and reducescycle/processing time, and thus manufacturing cost and capital. Thisapproach also reduces scale-up issues since scale-up is as simple asreplicating the number of tubes or syringes required to meet thethroughput requirements.

(b) Radio Frequency excitation of the plasma allows energy to beimparted to the ionized gas with little heating of the part. Unlikemicrowave excitation energies, typically used in PECVD, which willimpart significant energy to water molecules in the part itself, radiofrequency will not preferentially heat the polymeric tubes or syringes.Controlled heat absorption is critical to prevent substrate temperatureincreases approaching plastic glass transition temperatures, causingloss of dimensional integrity (collapse under vacuum).

(c) Single layer gas barrier coating—the new technology can generate asingle layer of silicon dioxide directly on the interior surface of thepart. Most other barrier technologies (thin film) require at least twolayers.

(d) Combination barrier-lubricity coatings—the new technology utilizes acombination SiO_(x)/ Si_(w)O_(x)C_(y)H_(z) coating to provide multipleperformance attributes (barrier/lubricity). The lubricity coating canalso be coated again with a barrier coating.

The plasma deposition technology in a preferred aspect utilizes a simplemanufacturing configuration. The system is based on a “puck,” which isused in transportation of tubes and syringes in and out of the coatingstation. The device-puck interface is critical, since oncecoating/characterization conditions are established at the pilot scale,there are no scaling issues when moving to full scale production; onesimply increases the number of pucks through the same process. The puckis manufactured from a polymeric material (e.g. Delrin™) to provide anelectrically insulated base. The container is mounted into the puck withthe largest opening sealing against an o-ring (mounted in the puckitself). The o-ring provides the vacuum seal between the part and thepuck so that the ambient air (principally nitrogen and oxygen with somewater vapor) can be removed (pressure reduced) and the process gasesintroduced. The puck has several key features in addition to the o-ringseal. The puck provides a means of connection to the vacuum pump (whichpumps away the atmospheric gases and the by-products of the silicondioxide reaction), a means of accurately aligning the gas inlet in thepart, and a means of providing a vacuum seal between the puck and gasinlet.

For SiO₂ deposition, HMDSO and oxygen gases are then admitted into thecontainer through the grounded gas inlet which extends up into the part.At this point, the puck and container are moved into the electrode area.The electrode is constructed from a conductive material (for examplecopper) and provides a tunnel through which the part passes. Theelectrode does not make physical contact with the container or the puckand is supported independently. An RF impedance matching network andpower supply are connected directly to the electrode. The power supplyprovides energy (at 13.56 MHz) to the impedance matched network. The RFmatching network acts to match the output impedance of the power supplyto the complex (capacitive and inductive) impedance of the ionizedgases. The matching network delivers maximum power delivery to theionized gas which ensures deposition of the silicon dioxide coating.

Once the container is coated (as the puck moves the container throughthe electrode channel—which is stationary), the gases are stopped andatmospheric air (or pure nitrogen) is allowed inside the puck/containerto bring it back to atmospheric pressure. At this time, the containercan be removed from the puck and moved to the next processing station.

The above describes clearly the means of coating a container having justone opening. Syringes require an additional step before and afterloading onto the puck. Since the syringes have openings at both ends(one for connection to a needle and the second for installation of aplunger), the needle end must be sealed prior to coating. The aboveprocess allows reaction gases to be admitted into the plastic partinterior, an electrical current to pass through the gas inside of thepart and a plasma to be established inside the part. The plasma (anionized composition of the HMDSO or OMCTS and oxygen gases) is whatdrives the chemistry and the deposition of the plasma coating.

In the method, the coating characteristics are advantageously set by oneor more of the following conditions: the plasma properties, the pressureunder which the plasma is applied, the power applied to generate theplasma, the presence and relative amount of O₂ in the gaseous reactant,the presence and relative amount of a carrier gas, e.g. of Argon in thegaseous reactant, the plasma volume, and the organosilicon precursor.Optionally, the coating characteristics are set by the presence andrelative amount of O₂ in the gaseous reactant, and/or the presence andrelative amount of the carrier gas (e.g. Argon) and/or the power appliedto generate the plasma.

In all embodiments of the present invention, the plasma is in anoptional aspect a non-hollow-cathode plasma, in particular when anSiO_(x) coating is formed. In an alternative optional aspect, there is ahollow-cathode plasma, in particular when a lubricity coating is formed.

In a further preferred aspect, the plasma is generated at reducedpressure (as compared to the ambient or atmospheric pressure).Optionally, the reduced pressure is less than 300 mTorr, optionally lessthan 200 mTorr, even optionally less than 100 mTorr.

The PECVD optionally is performed by energizing the gaseous reactantcontaining the precursor with electrodes powered at a frequency atmicrowave or radio frequency, and optionally at a radio frequency. Theradio frequency preferred to perform an embodiment of the invention willalso be addressed as “RF frequency”. A typical radio frequency range forperforming the present invention is a frequency of from 10 kHz to lessthan 300 MHz, optionally from 1 to 50 MHz, even optionally from 10 to 15MHz. A frequency of 13.56 MHz is most preferred, this being a governmentsanctioned frequency for conducting PECVD work.

There are several advantages for using a RF power source versus amicrowave source: Since RF operates a lower power, there is less heatingof the substrate/vessel. Because the focus of the present invention isputting a plasma coating on plastic substrates, lower processingtemperature are desired to prevent melting/distortion of the substrate.To prevent substrate overheating when using microwave PECVD, themicrowave PECVD is applied in short bursts, by pulsing the power. Thepower pulsing extends the cycle time for the coating, which is undesiredin the present invention. The higher frequency microwave can also causeoffgassing of volatile substances like residual water, oligomers andother materials in the plastic substrate. This offgassing can interferewith the PECVD coating. A major concern with using microwave for PECVDis delamination of the coating from the substrate. Delamination occursbecause the microwaves change the surface of the substrate prior todepositing the coating layer. To mitigate the possibility ofdelamination, interface coating layers have been developed for microwavePECVD to achieve good bonding between the coating and the substrate. Nosuch interface coating layer or coating is needed with RF PECVD as thereis no risk of delamination. Finally, the lubricity layer or coating andhydrophobic layer or coating according to the present invention areadvantageously applied using lower power. RF power operates at lowerpower and provides more control over the PECVD process than microwavepower. Nonetheless, microwave power, though less preferred, is usableunder suitable process conditions.

Furthermore, for all PECVD methods described herein, there is a specificcorrelation between the power (in Watts) used to generate the plasma andthe volume of the lumen wherein the plasma is generated. Typically, thelumen is the lumen of a vessel coated according to the presentinvention. The RF power should scale with the volume of the vessel ifthe same electrode system is employed. Once the composition of a gaseousreactant, for example the ratio of the precursor to O₂, and all otherparameters of the PECVD coating method but the power have been set, theywill typically not change when the geometry of a vessel is maintainedand only its volume is varied. In this case, the power will be directlyproportional to the volume. Thus, starting from the power to volumeratios provided by present description, the power which has to beapplied in order to achieve the same or a similar coating in a vessel ofsame geometry, but different size, can easily be found. The influence ofthe vessel geometry on the power to be applied is illustrated by theresults of the Examples for tubes in comparison to the Examples forsyringe barrels.

For any coating of the present invention, the plasma is generated withelectrodes powered with sufficient power to form a coating on thesubstrate surface. For a lubricity layer or coating, or hydrophobiclayer or coating (one layer may also be both lubricant and hydrophobic),in the method according to an embodiment of the invention the plasma isoptionally generated

(i) with electrodes supplied with an electric power of from 0.1 to 25 W,optionally from 1 to 22 W, optionally from 1 to 10 W, even optionallyfrom 1 to 5 W, optionally from 2 to 4 W, for example of 3 W, optionallyfrom 3 to 17 W, even optionally from 5 to 14 W, for example 6 or 7.5 W,optionally from 7 to 11 W, for example of 8 W.; and/or (ii) wherein theratio of the electrode power to the plasma volume is less than 10 W/ml,optionally is from 6 W/ml to 0.1 W/ml, optionally is from 5 W/ml to 0.1W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally is from 3 W/mlto 0.2 W/ml, optionally is from 2 W/ml to 0.2 W/ml.

Low power levels are believed by the inventors to be most advantageous(e.g. power levels of from 2 to 3.5 W and the power levels given in theExamples) to prepare a lubricity coating.

For a barrier coating or SiO_(x) coating, the plasma is optionallygenerated

(i) with electrodes supplied with an electric power of from 8 to 500 W,optionally from 20 to 400 W, optionally from 35 to 350 W, evenoptionally from 44 to 300 W, optionally from 44 to 70 W; and/or

(ii) the ratio of the electrode power to the plasma volume is equal ormore than 5 W/ml, optionally is from 6 W/ml to 150 W/ml, optionally isfrom 7 W/ml to 100 W/ml, optionally from 7 W/ml to 20 W/ml.

Low power levels are believed by the inventors to be most advantageous(e.g. power levels of from 2 to 3.5 W and the power levels given in theExamples) to prepare a lubricity coating. These power levels aresuitable for applying lubricity coatings to syringes and sample tubesand vessels of similar geometry having a void volume of 1 to 3 mL inwhich PECVD plasma is generated. It is contemplated that for larger orsmaller objects the power applied should be increased or reducedaccordingly to scale the process to the size of the substrate.

The vessel geometry can also influence the choice of the gas inlet usedfor the PECVD coating. In a particular aspect, a syringe can be coatedwith an open tube inlet, and a tube can be coated with a gas inlethaving small holes which is extended into the tube.

The power (in Watts) used for PECVD also has an influence on the coatingproperties. Typically, an increase of the power will increase thebarrier properties of the coating, and a decrease of the power willincrease the lubricity and hydrophobicity of the coating. This isdemonstrated in several Examples, in particular in Examples E to V. Itis also demonstrated in Examples of EP 2 251 455 A2, to which explicitreference is made herewith.

A further parameter determining the coating properties is the ratio ofO₂ (or another oxidizing agent) to the precursor (e.g. organosiliconprecursor) in the gaseous reactant used for generating the plasma.Typically, an increase of the O₂ ratio in the gaseous reactant willincrease the barrier properties of the coating, and a decrease of the O₂ratio will increase the lubricity and hydrophobicity of the coating. Ifa lubricity layer or coating is desired, then O₂ is optionally presentin a volume-volume ratio to the gaseous reactant of from 0:1 to 5:1,optionally from 0:1 to 1:1, even optionally from 0:1 to 0.5:1 or evenfrom 0:1 to 0.1:1. It is preferred that some O₂ is present, optionallyin an amount of from 0.01:1 to 0.5:1, even optionally from 0.05:1 to0.4:1, in particular from 0.1:1 to 0.2:1 in relation to theorganosilicon precursor. The presence of O₂ in a volume of about 5% toabout 35% (v/v in sccm) in relation to the organosilicon precursor, inparticular of about 10% to about 20% and in a ratio as given in theExamples is specifically suitable to achieve a lubricity coating.

If, on the other hand, a barrier or SiO_(x) coating is desired, then theO₂ is optionally present in a volume : volume ratio to the gaseousreactant of from 1:1 to 100:1 in relation to the silicon containingprecursor, optionally in a ratio of from 5:1 to 30:1, optionally in aratio of from 10:1 to 20:1, even optionally in a ratio of 15:1.

V.A. PECVD to Apply SiO_(x) Barrier Coating, Using Plasma that isSubstantially Free of Hollow Cathode Plasma

V.A. A specific embodiment encompasses a method of applying a barriercoating of SiO_(x), defined in this specification (unless otherwisespecified in a particular instance) as a coating containing silicon,oxygen, and optionally other elements, in which x, the ratio of oxygento silicon atoms, is from about 1.5 to about 2.9, or 1.5 to about 2.6,or about 2. These alternative definitions of x apply to any use of theterm SiO_(x) in this specification. The barrier coating is applied tothe interior of a vessel, for example a sample collection tube, asyringe barrel, or another type of vessel. The method includes severalsteps.

V.A. A vessel wall is provided, as is a reaction mixture comprisingplasma forming gas, i.e. an organosilicon compound gas, optionally anoxidizing gas, and optionally a hydrocarbon gas.

V.A. Plasma is formed in the reaction mixture that is substantially freeof hollow cathode plasma. The vessel wall is contacted with the reactionmixture, and the coating of SiO_(x) is deposited on at least a portionof the vessel wall.

V.A. In certain embodiments, the generation of a uniform plasmathroughout the portion of the vessel to be coated is contemplated, as ithas been found in certain instances to generate an SiO_(x) coatingproviding a better barrier against oxygen. Uniform plasma means regularplasma that does not include a substantial amount of hollow cathodeplasma (which has a higher emission intensity than regular plasma and ismanifested as a localized area of higher intensity interrupting the moreuniform intensity of the regular plasma).

V.A. The hollow cathode effect is generated by a pair of conductivesurfaces opposing each other with the same negative potential withrespect to a common anode. If the spacing is made (depending on thepressure and gas type) such that the space charge sheaths overlap,electrons start to oscillate between the reflecting potentials of theopposite wall sheaths leading to multiple collisions as the electronsare accelerated by the potential gradient across the sheath region. Theelectrons are confined in the space charge sheath overlap which resultsin very high ionization and high ion density plasmas. This phenomenon isdescribed as the hollow cathode effect. Those skilled in the art areable to vary the processing conditions, such as the power level and thefeed rates or pressure of the gases, to form uniform plasma throughoutor to form plasma including various degrees of hollow cathode plasma.

V.A. The plasma is typically generated using RF energy for the reasonsgiven above. In an alternate, but less typical method, microwave energycan be used to generate the plasma in a PECVD process. The processingconditions can be different, however, as microwave energy applied to athermoplastic vessel will excite (vibrate) water molecules. Since thereis a small amount of water in all plastic materials, the microwaves willheat the plastic. As the plastic heats, the large driving force createdby the vacuum inside of the device relative to atmospheric pressureoutside the device will pull free or easily desorb materials to theinterior surface 88 where they will either become volatile or will beweakly bound to the surface. The weakly bound materials will then createan interface that can hinder subsequent coatings (deposited from theplasma) from adhering to the plastic interior surface 88 of the device.

V.A. As one way to negate this coating hindering effect, a coating canbe deposited at very low power (in the example above 5 to 20 Watts at2.45 GHz) creating a cap onto which subsequent coatings can adhere. Thisresults in a two-step coating process (and two coating layers). In theexample above, the initial gas flows (for the capping layer) can bechanged to 2 sccm (“standard cubic centimeters per minute”) HMDSO and 20sccm oxygen with a process power of 5 to 20 Watts for approximately 2-10seconds. Then the gases can be adjusted to the flows in the exampleabove and the power level increased to 20-50 Watts so that an SiO_(x)coating, in which x in this formula is from about 1.5 to about 2.9,alternatively from about 1.5 to about 2.6, alternatively about 2, can bedeposited. Note that the capping layer or coating might provide littleto no functionality in certain embodiments, except to stop materialsfrom migrating to the vessel interior surface 88 during the higher powerSiO_(x) coating deposition. Note also that migration of easily desorbedmaterials in the device walls typically is not an issue at lowerfrequencies such as most of the RF range, since the lower frequencies donot excite (vibrate) molecular species.

V.A. As another way to negate the coating hindering effect describedabove, the vessel 80 can be dried to remove embedded water beforeapplying microwave energy. Desiccation or drying of the vessel 80 can beaccomplished, for example, by thermally heating the vessel 80, as byusing an electric heater or forced air heating. Desiccation or drying ofthe vessel 80 also can be accomplished by exposing the interior of thevessel 80, or gas contacting the interior of the vessel 80, to adesiccant. Other expedients for drying the vessel, such as vacuumdrying, can also be used. These expedients can be carried out in one ormore of the stations or devices illustrated or by a separate station ordevice.

V.A. Additionally, the coating hindering effect described above can beaddressed by selection or processing of the resin from which the vessels80 are molded to minimize the water content of the resin.

V.B. PECVD Coating Restricted Opening of Vessel (Syringe Capillary)

V.B. FIGS. 8 and 9 show a method and apparatus generally indicated at290 for coating an inner surface 292 of a restricted opening 294 of agenerally tubular vessel 250 to be processed, for example the restrictedfront opening 294 of a syringe barrel 250, by PECVD. The previouslydescribed process is modified by connecting the restricted opening 294to a processing vessel 296 and optionally making certain othermodifications.

V.B. The generally tubular vessel 250 to be processed includes an outersurface 298, an inner or interior surface 254 defining a lumen 300, alarger opening 302 having an inner diameter, and a restricted opening294 that is defined by an inner surface 292 and has an inner diametersmaller than the inner diameter of the larger opening 302.

V.B. The processing vessel 296 has a lumen 304 and a processing vesselopening 306, which optionally is the only opening, although in otherembodiments a second opening can be provided that optionally is closedoff during processing. The processing vessel opening 306 is connectedwith the restricted opening 294 of the vessel 250 to be processed toestablish communication between the lumen 300 of the vessel 250 to beprocessed and the processing vessel lumen via the restricted opening294.

V.B. At least a partial vacuum is drawn within the lumen 300 of thevessel 250 to be processed and lumen 304 of the processing vessel 296. APECVD reactant is flowed from the gas source 144 through the firstopening 302, then through the lumen 300 of the vessel 250 to beprocessed, then through the restricted opening 294, then into the lumen304 of the processing vessel 296.

V.B. The PECVD reactant can be introduced through the larger opening 302of the vessel 250 by providing a generally tubular inner electrode 308having an interior passage 310, a proximal end 312, a distal end 314,and a distal opening 316, in an alternative embodiment multiple distalopenings can be provided adjacent to the distal end 314 andcommunicating with the interior passage 310. The distal end of theelectrode 308 can be placed adjacent to or into the larger opening 302of the vessel 250 to be processed. A reactant gas can be fed through thedistal opening 316 of the electrode 308 into the lumen 300 of the vessel250 to be processed. The reactant will flow through the restrictedopening 294, then into the lumen 304, to the extent the PECVD reactantis provided at a higher pressure than the vacuum initially drawn beforeintroducing the PECVD reactant.

V.B. Plasma 318 is generated adjacent to the restricted opening 294under conditions effective to deposit a coating of a PECVD reactionproduct on the inner surface 292 of the restricted opening 294. In theembodiment shown in FIG. 8, the plasma is generated by feeding RF energyto the generally U-shaped outer electrode 160 and grounding the innerelectrode 308. The feed and ground connections to the electrodes couldalso be reversed, though this reversal can introduce complexity if thevessel 250 to be processed, and thus also the inner electrode 308, aremoving through the U-shaped outer electrode while the plasma is beinggenerated.

An aspect of the invention is a syringe including a needle and a barrel(a “staked needle syringe”) as described in U.S. Ser. No. 61/359,434,filed Jun. 29, 2010. The needle of this aspect of the invention has anoutside surface, a delivery outlet at one end, a base at the other end,and an internal passage extending from the base to the delivery outlet.The barrel has a, for example generally cylindrical, interior surfacedefining a lumen. The barrel also has a front passage molded around andin fluid-sealing contact with the outside surface of the needle.

The syringe of any “staked needle” embodiment optionally can furtherinclude a cap configured to isolate the delivery outlet of the needlefrom ambient air.

The cap of any “staked needle” embodiment optionally can further includea lumen having an opening defined by a rim and sized to receive thedelivery outlet, and the rim can be seatable against an exterior portionof the barrel.

In the syringe of any “staked needle” embodiment, the barrel optionallycan further include a generally hemispheric interior surface portionadjacent to its front passage.

In the syringe of any “staked needle” embodiment, the base of the needleoptionally can be at least substantially flush with the hemisphericinterior surface portion of the barrel.

The syringe of any “staked needle” embodiment optionally can furtherinclude a PECVD-applied barrier coating on at least the hemisphericinterior surface portion of the barrel.

In the syringe of any “staked needle” embodiment, the barrier coatingoptionally can extend over at least a portion of the generallycylindrical interior surface portion of the barrel.

In the syringe of any “staked needle” embodiment, the barrier coatingoptionally can form a barrier between the base of the needle and thegenerally cylindrical interior surface portion of the barrel.

In the “staked needle” embodiment of FIG. 24, the cap 7126 is held inplace on the nose 71110 of the syringe 7120 by a conventional Luer lockarrangement. The tapered nose 71110 of the syringe mates with acorresponding tapered throat 71112 of the cap 7126, and the syringe hasa collar 71114 with an interior thread 71116 receiving the dogs 71118and 71120 of the cap 7126 to lock the tapers 71110 and 71112 together.The cap 7126 can be substantially rigid.

Referring now to FIGS. 25A, 25B, and 25C, a variation on the syringebarrel 71122 and cap 71124 of the “staked needle” embodiment is shown.In this embodiment, the cap 71124 includes a flexible lip seal 7172 atits base to form a moisture-tight seal with the syringe barrel 71122.

Optionally in the “staked needle” embodiments of FIGS. 24 and 25A, 25B,and 25C, the caps 7126 and 71124 can withstand vacuum during the PECVDcoating process. The caps 7126 and 71124 can be made of LDPE.Alternative rigid plastic materials can be used as well, for examplepolypropylene. Additional sealing elements can be provided as well.

In another option of the “staked needle” embodiment, illustrated in FIG.26, the cap 71126 is flexible, and is designed to seal around the topend of the syringe 7120. A deformable material—like a rubber or athermoplastic elastomer (TPE) can be used for the cap 71126. PreferredTPE materials include fluoroelastomers, and in particular, medical gradefluoroelastomers. Examples include VITON® and TECHNOFLON®. VITON® ispreferable in some embodiments. An example of a suitable rubber is EPDMrubber.

During molding, in certain “staked needle” embodiments (illustrated forexample in FIG. 26) a small amount of the cap material 71132 will bedrawn into the tip or delivery outlet 7134 of the needle 7122 to createa seal. The material 71132 should have a durometer such as to permit anappropriate amount of material to be drawn into the needle 7122, and tocause the material drawn into the needle 7122 to continue to adhere tothe cap 71126 when it is removed, unplugging the needle 7122 for use.

In other “staked needle” embodiments, the cap material 71132 can blockthe delivery outlet 7134 of the needle 7122 without being drawn into thedelivery outlet 7134. Suitable material selection to accomplish thedesired purposes is within the capabilities of a person of ordinaryskill in the art.

An additional seal can be created by coupling an undercut 71134 formedin the syringe barrel and projections 71138 in the interior of the cap71126, defining a coupling to retain the cap 71126. Alternative “stakedneedle” embodiments can include either one or both of the sealsdescribed above.

Optionally, with reference to FIGS. 25A, 25B, AND 25C, the cap 71124 canhave a base 7168 and a coupling 7170 configured for securing the cap7126 in a seated position on the barrel. Alternatively or in addition, aflexible lip seal 7172 can optionally be provided at the base 7168 ofthe cap 71124 for seating against the barrel 71122 when the cap 71124 issecured on the barrel 71122.

Optionally, referring now to FIG. 26, the delivery outlet 7134 of theneedle 7122 can be seated on the cap 71126 when the cap 7126 is securedon the barrel. This expedient is useful for sealing the delivery outlet7134 against the ingress or egress of air or other fluids, when that isdesired.

Optionally, in the “staked needle” embodiment the coupling 7170 caninclude a detent or groove 7174 on one of the barrel 71122 and the cap71124 and a projection or rib 7176 on the other of the barrel 71122 andthe cap 71124, the projection 7176 being adapted to mate with the detent7174 when the cap 7126 is in its seated position on the barrel. In onecontemplated embodiment, a detent 7174 can be on the barrel and aprojection 7176 can be on the cap 7126. In another contemplatedembodiment, a detent 7174 can be on the cap 7126 and a projection 7176can be on the barrel. In yet another contemplated embodiment, a firstdetent 7174 can be on the barrel and a first projection 7176 mating withthe detent 7174 can be on the cap 7126, while a second detent 7175 canbe on the cap 7126 and the mating second projection 7177 can be on thebarrel. A detent 7174 can be molded in the syringe barrel as an undercutby incorporating side draws such as 7192 and 7194 in the mold.

The detents 7174 mate with the complementary projections 7176 toassemble (snap) the cap 7126 onto the syringe 7120. In this respect thecap 7126 is desirably flexible enough to allow sufficient deformationfor a snapping engagement of the detents 7174 and projections 7176.

The caps in the “staked needle” embodiment such as 7126, 71124, and71126 can be injection molded or otherwise formed, for example fromthermoplastic material. Several examples of suitable thermoplasticmaterial are a polyolefin, for example a cyclic olefin polymer (COP), acyclic olefin copolymer (COC), polypropylene, or polyethylene. The cap7126 can contain or be made of a thermoplastic elastomer (TPE) or otherelastomeric material. The cap 7126 can also be made of polyethyleneterephthalate (PET), polycarbonate resin, or any other suitablematerial. Optionally, a material for the cap 7126 can be selected thatcan withstand vacuum and maintain sterility within the syringe 7120.

V.B. The plasma 318 generated in the vessel 250 during at least aportion of processing can include hollow cathode plasma generated insidethe restricted opening 294 and/or the processing vessel lumen 304. Thegeneration of hollow cathode plasma 318 can contribute to the ability tosuccessfully apply a barrier coating at the restricted opening 294,although the invention is not limited according to the accuracy orapplicability of this theory of operation. Thus, in one contemplatedmode of operation, the processing can be carried out partially underconditions generating a uniform plasma throughout the vessel 250 and thegas inlet, and partially under conditions generating a hollow cathodeplasma, for example adjacent to the restricted opening 294.

V.B. The process is desirably operated under such conditions, asexplained here and shown in the drawings, that the plasma 318 extendssubstantially throughout the syringe lumen 300 and the restrictedopening 294. The plasma 318 also desirably extends substantiallythroughout the syringe lumen 300, the restricted opening 294, and thelumen 304 of the processing vessel 296. This assumes that a uniformcoating of the interior 254 of the vessel 250 is desired. In otherembodiments non-uniform plasma can be desired.

V.B. It is generally desirable that the plasma 318 have a substantiallyuniform color throughout the syringe lumen 300 and the restrictedopening 294 during processing, and optionally a substantially uniformcolor substantially throughout the syringe lumen 300, the restrictedopening 294, and the lumen 304 of the processing vessel 296. The plasmadesirably is substantially stable throughout the syringe lumen 300 andthe restricted opening 294, and optionally also throughout the lumen 304of the processing vessel 296.

V.B. The order of steps in this method is not contemplated to becritical.

V.B. In the embodiment of FIGS. 8 and 9, the restricted opening 294 hasa first fitting 332 and the processing vessel opening 306 has a secondfitting 334 adapted to seat to the first fitting 332 to establishcommunication between the lumen 304 of the processing vessel 296 and thelumen 300 of the vessel 250 to be processed.

V.B. In the embodiment of FIGS. 8 and 9, the first and second fittingsare male and female Luer lock fittings 332 and 334, respectivelyintegral with the structure defining the restricted opening 294 and theprocessing vessel opening 306. One of the fittings, in this case themale Luer lock fitting 332, comprises a locking collar 336 with athreaded inner surface and defining an axially facing, generally annularfirst abutment 338 and the other fitting 334 comprises an axiallyfacing, generally annular second abutment 340 facing the first abutment338 when the fittings 332 and 334 are engaged.

V.B. In the illustrated embodiment a seal, for example an O-ring 342 canbe positioned between the first and second fittings 332 and 334. Forexample, an annular seal can be engaged between the first and secondabutments 338 and 340. The female Luer fitting 334 also includes dogs344 that engage the threaded inner surface of the locking collar 336 tocapture the O-ring 342 between the first and second fittings 332 and334. Optionally, the communication established between the lumen 300 ofthe vessel 250 to be processed and the lumen 304 of the processingvessel 296 via the restricted opening 294 is at least substantially leakproof.

V.B. As a further option, either or both of the Luer lock fittings 332and 334 can be made of electrically conductive material, for examplestainless steel. This construction material forming or adjacent to therestricted opening 294 might contribute to formation of the plasma inthe restricted opening 294.

V.B. The desirable volume of the lumen 304 of the processing vessel 296is contemplated to be a trade-off between a small volume that will notdivert much of the reactant flow away from the product surfaces desiredto be coated and a large volume that will support a generous reactantgas flow rate through the restricted opening 294 before filling thelumen 304 sufficiently to reduce that flow rate to a less desirablevalue (by reducing the pressure difference across the restricted opening294). The contemplated volume of the lumen 304, in an embodiment, isless than three times the volume of the lumen 300 of the vessel 250 tobe processed, or less than two times the volume of the lumen 300 of thevessel 250 to be processed, or less than the volume of the lumen 300 ofthe vessel 250 to be processed, or less than 50% of the volume of thelumen 300 of the vessel 250 to be processed, or less than 25% of thevolume of the lumen 300 of the vessel 250 to be processed. Othereffective relationships of the volumes of the respective lumens are alsocontemplated.

V.B. The inventors have found that the uniformity of coating can beimproved in certain embodiments by repositioning the distal end of theelectrode 308 relative to the vessel 250 so it does not penetrate as farinto the lumen 300 of the vessel 250 as the position of the innerelectrode shown in previous Figures. For example, although in certainembodiments the distal opening 316 can be positioned adjacent to therestricted opening 294, in other embodiments the distal opening 316 canbe positioned less than 7/8 the distance, optionally less than ¾ thedistance, optionally less than half the distance to the restrictedopening 294 from the larger opening 302 of the vessel to be processedwhile feeding the reactant gas. Or, the distal opening 316 can bepositioned less than 40%, less than 30%, less than 20%, less than 15%,less than 10%, less than 8%, less than 6%, less than 4%, less than 2%,or less than 1% of the distance to the restricted opening 294 from thelarger opening of the vessel to be processed while feeding the reactantgas.

V.B. Or, the distal end of the electrode 308 can be positioned eitherslightly inside or outside or flush with the larger opening 302 of thevessel 250 to be processed while communicating with, and feeding thereactant gas to, the interior of the vessel 250. The positioning of thedistal opening 316 relative to the vessel 250 to be processed can beoptimized for particular dimensions and other conditions of treatment bytesting it at various positions. One particular position of theelectrode 308 contemplated for treating syringe barrels 250 is with thedistal end 314 penetrating about a quarter inch (about 6 mm) into thevessel lumen 300 above the larger opening 302.

V.B. The inventors presently contemplate that it is advantageous toplace at least the distal end 314 of the electrode 308 within the vessel250 so it will function suitably as an electrode, though that is notnecessarily a requirement. Surprisingly, the plasma 318 generated in thevessel 250 can be made more uniform, extending through the restrictedopening 294 into the processing vessel lumen 304, with less penetrationof the electrode 308 into the lumen 300 than has previously beenemployed. With other arrangements, such as processing a closed-endedvessel, the distal end 314 of the electrode 308 commonly is placedcloser to the closed end of the vessel than to its entrance.

V.B. Or, the distal end 314 of the electrode 308 can be positioned atthe restricted opening 294 or beyond the restricted opening 294, forexample within the processing vessel lumen 304. Various expedients canoptionally be provided, such as shaping the processing vessel 296 toimprove the gas flow through the restricted opening 294.

V.B. In yet another contemplated embodiment, the inner electrode 308, asin FIG. 8, can be moved during processing, for example, at firstextending into the processing vessel lumen 304, then being withdrawnprogressively proximally as the process proceeds. This expedient isparticularly contemplated if the vessel 250, under the selectedprocessing conditions, is long, and movement of the inner electrodefacilitates more uniform treatment of the interior surface 254. Usingthis expedient, the processing conditions, such as the gas feed rate,the vacuum draw rate, the electrical energy applied to the outerelectrode 160, the rate of withdrawing the inner electrode 308, or otherfactors can be varied as the process proceeds, customizing the processto different parts of a vessel to be treated.

V.B. Conveniently, as in the other processes described in thisspecification, the larger opening of the generally tubular vessel 250 tobe processed can be placed on a vessel support 320, as by seating thelarger opening 302 of the vessel 250 to be processed on a port 322 ofthe vessel support 320. Then the inner electrode 308 can be positionedwithin the vessel 250 seated on the vessel support 320 before drawing atleast a partial vacuum within the lumen 300 of the vessel 250 to beprocessed.

V.C. Method of Applying a Lubricity Coating; and Lubricity Coating

V.C. The main embodiments of present invention are a method of applyinga lubricity layer or coating derived from an organosilicon precursor,and the resulting coating and coated item. A “lubricity layer” or anysimilar term is generally defined as a coating that reduces thefrictional resistance of the coated surface, relative to the uncoatedsurface. If the coated object is a syringe (or syringe part, e.g.syringe barrel) or any other item generally containing a plunger ormovable part in sliding contact with the coated surface, the frictionalresistance has two main aspects—breakout force and plunger slidingforce.

The plunger sliding force test is a specialized test of the coefficientof sliding friction of the plunger within a syringe, accounting for thefact that the normal force associated with a coefficient of slidingfriction as usually measured on a flat surface is addressed bystandardizing the fit between the plunger or other sliding element andthe tube or other vessel within which it slides. The parallel forceassociated with a coefficient of sliding friction as usually measured iscomparable to the plunger sliding force measured as described in thisspecification. Plunger sliding force can be measured, for example, asprovided in the ISO 7886-1:1993 test.

The plunger sliding force test can also be adapted to measure othertypes of frictional resistance, for example the friction retaining astopper within a tube, by suitable variations on the apparatus andprocedure. In one embodiment, the plunger can be replaced by a closureand the withdrawing force to remove or insert the closure can bemeasured as the counterpart of plunger sliding force.

Also or instead of the plunger sliding force, the breakout force can bemeasured. The breakout force is the force required to start a stationaryplunger moving within a syringe barrel, or the comparable force requiredto unseat a seated, stationary closure and begin its movement. Thebreakout force is measured by applying a force to the plunger thatstarts at zero or a low value and increases until the plunger beginsmoving. The breakout force tends to increase with storage of a syringe,after the prefilled syringe plunger has pushed away the interveninglubricant or adhered to the barrel due to decomposition of the lubricantbetween the plunger and the barrel. The breakout force is the forceneeded to overcome “sticktion,” an industry term for the adhesionbetween the plunger and barrel that needs to be overcome to break outthe plunger and allow it to begin moving.

The break loose force (Fi) and the glide force (Fm) are importantperformance measures for the effectiveness of a lubricity coating. ForFi and Fm, it is desired to have a low, but not too low value. With toolow Fi, which means a too low level of resistance (the extreme beingzero), premature/unintended flow may occur, which might e.g. lead to anunintentional premature or uncontrolled discharge of the content of aprefilled syringe.

In order to achieve a sufficient lubricity (e.g. to ensure that asyringe plunger can be moved in the syringe, but to avoid uncontrolledmovement of the plunger), the following ranges of Fi and Fm should beadvantageously maintained:

-   Fi: 2.5 to 5 lbs, preferably 2.7 to 4.9 lbs, and in particular 2.9    to 4.7 lbs;-   Fm: 2.5 to 8.0 lbs, preferably 3.3 to 7.6 lbs, and in particular 3.3    to 4 lbs.

Further advantageous Fi and Fm values can be found in the Tables of theExamples.

The lubricity coating optionally provides a consistent plunger forcethat reduces the difference between the break loose force (Fi) and theglide force (Fm).

V.C. Some utilities of coating a vessel in whole or in part with alubricity layer, such as selectively at surfaces contacted in slidingrelation to other parts, is to ease the insertion or removal of astopper or passage of a sliding element such as a piston in a syringe ora stopper in a sample tube. The vessel can be made of glass or a polymermaterial such as polyester, for example polyethylene terephthalate(PET), a cyclic olefin copolymer (COC), an olefin such as polypropylene,or other materials. COC is particularly suitable for syringes. Applyinga lubricity layer or coating by PECVD can avoid or reduce the need tocoat the vessel wall or closure with a sprayed, dipped, or otherwiseapplied organosilicon or other lubricant that commonly is applied in afar larger quantity than would be deposited by a PECVD process.

V.C. In any of the above embodiments V.C., a plasma is formed in thevicinity of the substrate.

In any of embodiments V.C., the precursor optionally can be provided inthe substantial absence of nitrogen. In any of embodiments V.C., theprecursor optionally can be provided at less than 1 Torr absolutepressure.

V.C. In any of embodiments V.C., the precursor optionally can beprovided to the vicinity of a plasma emission.

V.C. In any of embodiments V.C., the coating optionally can be appliedto the substrate at a thickness of 1 to 5000 nm, or 10 to 1000 nm, or 10to 500 nm, or 10 to 200 nm, or 20 to 100 nm, or 30 to 1000 nm, or 30 to500 nm thick. A typical thickness is from 30 to 1000 nm or from 20 to100 nm, a very typical thickness is from 80 to 150 nm. These ranges arerepresenting average thicknesses, as a certain roughness may enhance thelubricious properties of the lubricity coating. Thus its thickness isadvantageously not uniform throughout the coating (see below). However,a uniformly thick lubricity coating is also considered.

The absolute thickness of the lubricity coating at single measurementpoints can be higher or lower than the range limits of the averagethickness, with maximum deviations of preferably +/−50%, more preferably+/−25% and even more preferably +/−15% from the average thickness.However, it typically varies within the thickness ranges given for theaverage thickness in this description.

The thickness of this and other coatings can be measured, for example,by transmission electron microscopy (TEM). An exemplary TEM image for alubricity coating is shown in FIG. 21. An exemplary TEM image for anSiO2 barrier coating (described in more detail elsewhere) is shown inFIG. 22.

V.C. The TEM can be carried out, for example, as follows. Samples can beprepared for Focused Ion Beam (FIB) cross-sectioning in two ways. Eitherthe samples can be first coated with a thin layer or coating of carbon(50-100 nm thick) and then coated with a sputtered layer or coating ofplatinum (50-100 nm thick) using a K575X Emitech coating system, or thesamples can be coated directly with the protective sputtered Pt layer.The coated samples can be placed in an FEI FIB200 FIB system. Anadditional layer or coating of platinum can be FIB-deposited byinjection of an oregano-metallic gas while rastering the 30 kV galliumion beam over the area of interest. The area of interest for each samplecan be chosen to be a location half way down the length of the syringebarrel. Thin cross sections measuring approximately 15 μm(“micrometers”) long, 2 μm wide and 15 μm deep can be extracted from thedie surface using a proprietary in-situ FIB lift-out technique. Thecross sections can be attached to a 200 mesh copper TEM grid usingFIB-deposited platinum. One or two windows in each section, measuring ˜8μm wide, can be thinned to electron transparency using the gallium ionbeam of the FEI FIB.

V.C. Cross-sectional image analysis of the prepared samples can beperformed utilizing either a Transmission Electron Microscope (TEM), ora Scanning Transmission Electron Microscope (STEM), or both. All imagingdata can be recorded digitally. For STEM imaging, the grid with thethinned foils can be transferred to a Hitachi HD2300 dedicated STEM.Scanning transmitted electron images can be acquired at appropriatemagnifications in atomic number contrast mode (ZC) and transmittedelectron mode (TE). The following instrument settings can be used.

Scanning Transmission Electron 1. Instrument MicroscopeManufacturer/Model Hitachi HD2300 Accelerating Voltage 200 kV ObjectiveAperture #2 Condenser Lens 1 Setting 1.672 Condenser Lens 2 Setting1.747 Approximate Objective Lens Setting 5.86 ZC Mode Projector Lens1.149 TE Mode Projector Lens 0.7 Image Acquisition Pixel Resolution 1280× 960 Acquisition Time 20 sec.(x4)

V.C. For TEM analysis the sample grids can be transferred to a HitachiHF2000 transmission electron microscope. Transmitted electron images canbe acquired at appropriate magnifications. The relevant instrumentsettings used during image acquisition can be those given below.

Transmission Electron Instrument Microscope Manufacturer/Model HitachiHF2000 Accelerating Voltage 200 kV Condenser Lens 1 0.78 Condenser Lens2 0 Objective Lens 6.34 Condenser Lens Aperture #1 Objective LensAperture for #3 imaging Selective Area Aperture for N/A SAD

V.C. In any of embodiments V.C., the substrate can comprise glass or apolymer, for example a polycarbonate polymer, an olefin polymer, acyclic olefin copolymer, a polypropylene polymer, a polyester polymer, apolyethylene terephthalate polymer or a combination of any two or moreof these.

V.C. In any of embodiments V.C., the PECVD optionally can be performedby energizing the gaseous reactant containing the precursor withelectrodes powered at a RF frequency as defined above, for example afrequency from 10 kHz to less than 300 MHz, optionally from 1 to 50 MHz,even optionally from 10 to 15 MHz, optionally a frequency of 13.56 MHz.

V.C. In any of embodiments V.C., the plasma can be generated byenergizing the gaseous reactant comprising the precursor with electrodessupplied with electric power sufficient to form a lubricity layer.Optionally, the plasma is generated by energizing the gaseous reactantcontaining the precursor with electrodes supplied with an electric powerof from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 1 to 10W, even optionally from 1 to 5 W, optionally from 2 to 4 W, for exampleof 3 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, forexample 6 or 7.5 W, optionally from 7 to 11 W, for example of 8 W. Theratio of the electrode power to the plasma volume can be less than 10W/ml, optionally is from 6 W/ml to 0.1 W/ml, optionally is from 5 W/mlto 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionally is from 2W/ml to 0.2 W/ml. Low power levels are believed by the inventors to bemost advantageous (e.g. power levels of from 2 to 3.5 W and the powerlevels given in the Examples) to prepare a lubricity coating. Thesepower levels are suitable for applying lubricity coatings to syringesand sample tubes and vessels of similar geometry having a void volume of1 to 3 mL in which PECVD plasma is generated. It is contemplated thatfor larger or smaller objects the power applied should be increased orreduced accordingly to scale the process to the size of the substrate.

V.C. In any of embodiments V.C., one preferred combination of processgases includes octamethylcyclotetrasiloxane (OMCTS) or another cyclicsiloxane as the precursor, in the presence of oxygen as the oxidizinggas and argon as the carrier gas. Without being bound to the accuracy ofthis theory, the inventors believe this particular combination iseffective for the following reasons.

V.C. It is believed that the OMCTS or other cyclic siloxane moleculeprovides several advantages over other siloxane materials. First, itsring structure results in a less dense coating (as compared to coatingsprepared from HMDSO). The molecule also allows selective ionization sothat the final structure and chemical composition of the coating can bedirectly controlled through the application of the plasma power. Otherorganosilicon molecules are readily ionized (fractured) so that it ismore difficult to retain the original structure of the molecule.

V.C. Since the addition of Argon gas improves the lubricity performance(see the working examples below), it is believed that additionalionization of the molecule in the presence of Argon contributes toproviding lubricity. The Si—O—Si bonds of the molecule have a high bondenergy followed by the Si—C, with the C—H bonds being the weakest.Lubricity appears to be achieved when a portion of the C—H bonds arebroken. This allows the connecting (cross-linking) of the structure asit grows. Addition of oxygen (with the Argon) is understood to enhancethis process. A small amount of oxygen can also provide C—O bonding towhich other molecules can bond. The combination of breaking C—H bondsand adding oxygen all at low pressure and power leads to a chemicalstructure that is solid while providing lubricity.

In a specific embodiment of the present invention, the lubricity canalso be influenced by the roughness of the lubricity coating whichresults from the PECVD process using the precursors and conditionsdescribed herein. It has now surprisingly been found in the context ofpresent invention by performing scanning electron microscopy (SEM) andatomic force microscopy (AFM), that a rough, non-continuous OMCTS plasmacoating offers lower plunger force (Fi, Fm) than a smooth, continuousOMCTS plasma coating. This is demonstrated by Examples O to V.

While not bound by theory, the inventors assume that this particulareffect could be, in part, based on one or both of the followingmechanistic effects:

(a) lower surface contact of the plunger with the lubricity coating(e.g. the circular rigid plunger surface contacting only the peaks of arough coating), either initially and/or throughout the plunger movement,resulting in overall lower contact and thus friction. (b) Upon plungermovement, the plunger causes the initial non-uniform, rough coating tobe spread and smoothed into the uncoated “valleys”.

The roughness of the lubricity coating is increased with decreasingpower (in Watts) energizing the plasma, and by the presence of O2 in theamounts described above. The roughness can be expressed as “RMSroughness” or “RMS” determined by AFM. RMS is the standard deviation ofthe difference between the highest and lowest points in an AFM image(the difference is designated as “Z”). It is calculated according to theformula:

Rq={Σ(Z1−Zavg)2/N}−2

-   where Zavg is the average Z value within the image; Z1 is the    current value of Z; and N is the number of points in the image.

The RMS range in this specific embodiment is typically from 7 to 20 nm,preferably from 12 to 20 nm. A lower RMS can, however, still lead tosatisfying lubricity properties.

V.C. One contemplated product optionally can be a syringe having abarrel treated by the method of any one or more of embodiments V.C. Saidsyringe can either have just a lubricity coating according to presentinvention, or it can have the lubricity coating and one or more othercoatings in addition, e.g. a SiO_(x) barrier coating under or over thelubricity coating.

V.D. Liquid-Applied Coatings

V.D. An example of a suitable barrier or other type of coating, usablein conjunction with the PECVD-applied coatings or other PECVD treatmentas disclosed here, can be a liquid barrier, lubricant, surface energytailoring, or other type of coating 90 applied to the interior surfaceof a vessel, either directly or with one or more interveningPECVD-applied coatings described in this specification, for exampleSiO_(x), a lubricity layer or coating according to present invention, orboth.

V.D. Suitable liquid barriers or other types of coatings 90 alsooptionally can be applied, for example, by applying a liquid monomer orother polymerizable or curable material to the interior surface of thevessel 80 and curing, polymerizing, or crosslinking the liquid monomerto form a solid polymer. Suitable liquid barrier or other types ofcoatings 90 can also be provided by applying a solvent-dispersed polymerto the surface 88 and removing the solvent.

V.D. Either of the above methods can include as a step forming a coating90 on the interior 88 of a vessel 80 via the vessel port 92 at aprocessing station or device 28. One example is applying a liquidcoating, for example of a curable monomer, prepolymer, or polymerdispersion, to the interior surface 88 of a vessel 80 and curing it toform a film that physically isolates the contents of the vessel 80 fromits interior surface 88. The prior art describes polymer coatingtechnology as suitable for coating plastic blood collection tubes. Forexample, the acrylic and polyvinylidene chloride (PVdC) coatingmaterials and coating methods described in U.S. Pat. 6,165,566, which ishereby incorporated by reference, optionally can be used.

V.D. Either of the above methods can also or include as a step forming acoating on the exterior outer wall of a vessel 80. The coatingoptionally can be a barrier coating, optionally an oxygen barriercoating, or optionally a water barrier coating. One example of asuitable coating is polyvinylidene chloride, which functions both as awater barrier and an oxygen barrier. Optionally, the barrier coating canbe applied as a water-based coating. The coating optionally can beapplied by dipping the vessel in it, spraying it on the vessel, or otherexpedients. A vessel having an exterior barrier coating as describedabove is also contemplated.

VII. PECVD Treated Vessels

VII. Vessels are contemplated having a barrier coating 90 (shown in FIG.1, for example), which can be an SiO_(x) coating applied to a thicknessof at least 2 nm, or at least 4 nm, or at least 7 nm, or at least 10 nm,or at least 20 nm, or at least 30 nm, or at least 40 nm, or at least 50nm, or at least 100 nm, or at least 150 nm, or at least 200 nm, or atleast 300 nm, or at least 400 nm, or at least 500 nm, or at least 600nm, or at least 700 nm, or at least 800 nm, or at least 900 nm. Thecoating can be up to 1000 nm, or at most 900 nm, or at most 800 nm, orat most 700 nm, or at most 600 nm, or at most 500 nm, or at most 400 nm,or at most 300 nm, or at most 200 nm, or at most 100 nm, or at most 90nm, or at most 80 nm, or at most 70 nm, or at most 60 nm, or at most 50nm, or at most 40 nm, or at most 30 nm, or at most 20 nm, or at most 10nm, or at most 5 nm thick. Specific thickness ranges composed of any oneof the minimum thicknesses expressed above, plus any equal or greaterone of the maximum thicknesses expressed above, are expresslycontemplated. The thickness of the SiO_(x) or other coating can bemeasured, for example, by transmission electron microscopy (TEM), andits composition can be measured by X-ray photoelectron spectroscopy(XPS).

VII. It is contemplated that the choice of the material to be barredfrom permeating the coating and the nature of the SiO_(x) coatingapplied can affect its barrier efficacy. For example, two examples ofmaterial commonly intended to be barred are oxygen and water/watervapor. Materials commonly are a better barrier to one than to the other.This is believed to be so at least in part because oxygen is transmittedthrough the coating by a different mechanism than water is transmitted.

VII. Oxygen transmission is affected by the physical features of thecoating, such as its thickness, the presence of cracks, and otherphysical details of the coating. Water transmission, on the other hand,is believed to commonly be affected by chemical factors, i.e. thematerial of which the coating is made, more than physical factors. Theinventors also believe that at least one of these chemical factors is asubstantial concentration of OH moieties in the coating, which leads toa higher transmission rate of water through the barrier. An SiO_(x)coating often contains OH moieties, and thus a physically sound coatingcontaining a high proportion of OH moieties is a better barrier tooxygen than to water. A physically sound carbon-based barrier, such asamorphous carbon or diamond-like carbon (DLC) commonly is a betterbarrier to water than is a SiO_(x) coating because the carbon-basedbarrier more commonly has a lower concentration of OH moieties.

VII. Other factors lead to a preference for an SiO_(x) coating, however,such as its oxygen barrier efficacy and its close chemical resemblanceto glass and quartz. Glass and quartz (when used as the base material ofa vessel) are two materials long known to present a very high barrier tooxygen and water transmission as well as substantial inertness to manymaterials commonly carried in vessels. Thus, it is commonly desirable tooptimize the water barrier properties such as the water vaportransmission rate (WVTR) of an SiO_(x) coating, rather than choosing adifferent or additional type of coating to serve as a water transmissionbarrier.

VII. Several ways contemplated to improve the WVTR of an SiO_(x) coatingare as follow.

VII. The concentration ratio of organic moieties (carbon and hydrogencompounds) to OH moieties in the deposited coating can be increased.This can be done, for example, by increasing the proportion of oxygen inthe feed gases (as by increasing the oxygen feed rate or by lowering thefeed rate of one or more other constituents). The lowered incidence ofOH moieties is believed to result from increasing the degree of reactionof the oxygen feed with the hydrogen in the silicone source to yieldmore volatile water in the PECVD exhaust and a lower concentration of OHmoieties trapped or incorporated in the coating.

VII. Higher energy can be applied in the PECVD process, either byraising the plasma generation power level, by applying the power for alonger period, or both. An increase in the applied energy must beemployed with care when used to coat a plastic tube or other device, asit also has a tendency to distort the vessel being treated, to theextent the tube absorbs the plasma generation power. This is why RFpower is contemplated in the context of present application. Distortionof the medical devices can be reduced or eliminated by employing theenergy in a series of two or more pulses separated by cooling time, bycooling the vessels while applying energy, by applying the coating in ashorter time (commonly thus making it thinner), by selecting a frequencyof the applied coating that is absorbed minimally by the base materialselected for being coated, and/or by applying more than one coating,with time in between the respective energy application steps. Forexample, high power pulsing can be used with a duty cycle of 1millisecond on, 99 milliseconds off, while continuing to feed thegaseous reactant or process gas. The gaseous reactant or process gas isthen the coolant, as it keeps flowing between pulses. Anotheralternative is to reconfigure the power applicator, as by adding magnetsto confine the plasma increase the effective power application (thepower that actually results in incremental coating, as opposed to wastepower that results in heating or unwanted coating). This expedientresults in the application of more coating-formation energy per totalWatt-hour of energy applied. See for example U.S. Pat. 5,904,952.

VII. An oxygen post-treatment of the coating can be applied to remove OHmoieties from the previously-deposited coating. This treatment is alsocontemplated to remove residual volatile organosilicon compounds orsilicones or oxidize the coating to form additional SiO_(x).

VII. The plastic base material tube can be preheated.

VII. A different volatile source of silicon, such ashexamethyldisilazane (HMDZ), can be used as part or all of the siliconefeed. It is contemplated that changing the feed gas to HMDZ will addressthe problem because this compound has no oxygen moieties in it, assupplied. It is contemplated that one source of OH moieties in theHMDSO-sourced coating is hydrogenation of at least some of the oxygenatoms present in unreacted HMDSO.

VII. A composite coating can be used, such as a carbon-based coatingcombined with SiOx. This can be done, for example, by changing thereaction conditions or by adding a substituted or unsubstitutedhydrocarbon, such as an alkane, alkene, or alkyne, to the feed gas aswell as an organosilicon-based compound. See for example U.S. Pat.5,904,952, which states in relevant part: “For example, inclusion of alower hydrocarbon such as propylene provides carbon moieties andimproves most properties of the deposited films (except for lighttransmission), and bonding analysis indicates the film to be silicondioxide in nature. Use of methane, methanol, or acetylene, however,produces films that are silicone in nature. The inclusion of a minoramount of gaseous nitrogen to the gas stream provides nitrogen moietiesin the deposited films and increases the deposition rate, improves thetransmission and reflection optical properties on glass, and varies theindex of refraction in response to varied amounts of N2. The addition ofnitrous oxide to the gas stream increases the deposition rate andimproves the optical properties, but tends to decrease the filmhardness.” Suitable hydrocarbons include methane, ethane, ethylene,propane, acetylene, or a combination of two or more of these.

VII. A diamond-like carbon (DLC) coating can be formed as the primary orsole coating deposited. This can be done, for example, by changing thereaction conditions or by feeding methane, hydrogen, and helium to aPECVD process. These reaction feeds have no oxygen, so no OH moietiescan be formed. For one example, an SiO_(x) coating can be applied on theinterior of a tube or syringe barrel and an outer DLC coating can beapplied on the exterior surface of a tube or syringe barrel. Or, theSiO_(x) and DLC coatings can both be applied as a single layer orcoating or plural layers of an interior tube or syringe barrel coating.

VII. Referring to FIG. 1, the barrier or other type of coating 90reduces the transmission of atmospheric gases into the vessel 80 throughits interior surface 88. Or, the barrier or other type of coating 90reduces the contact of the contents of the vessel 80 with the interiorsurface 88. The barrier or other type of coating can comprise, forexample, SiO_(x), amorphous (for example, diamond-like) carbon, or acombination of these.

VII. Any coating described herein can be used for coating a surface, forexample a plastic surface. It can further be used as a barrier layer,for example as a barrier against a gas or liquid, optionally againstwater vapor, oxygen and/or air. It can also be used for preventing orreducing mechanical and/or chemical effects which the coated surfacewould have on a compound or composition if the surface were uncoated.For example, it can prevent or reduce the precipitation of a compound orcomposition, for example insulin precipitation or blood clotting orplatelet activation.

VII.A. Coated Vessels

The coatings described herein can be applied to a variety of vesselsmade from plastic or glass, most prominently to plastic tubes andsyringes. A process is contemplated for applying a lubricity layer orcoating on a substrate, for example the interior of the barrel of asyringe, comprising applying one of the described precursors on or inthe vicinity of a substrate at a thickness of 1 to 5000 nm, or 10 to1000 nm, or 10 to 500 nm, or 10 to 200 nm, or 20 to 100 nm, or 30 to1000 nm, or 30 to 500 nm thick, or 30 to 1000 nm, or 20 to 100 nm, or 80to 150 nm, and crosslinking or polymerizing (or both) the coating,optionally in a PECVD process, to provide a lubricated surface. Thecoating applied by this process is also contemplated to be new.

A coating of Si_(w)O_(x)C_(y)H_(z) as defined in the Definition Sectioncan have utility as a hydrophobic layer. Coatings of this kind arecontemplated to be hydrophobic, independent of whether they function aslubricity layers. A coating or treatment is defined as “hydrophobic” ifit lowers the wetting tension of a surface, compared to thecorresponding uncoated or untreated surface. Hydrophobicity is thus afunction of both the untreated substrate and the treatment.

The degree of hydrophobicity of a coating can be varied by varying itscomposition, properties, or deposition method. For example, a coating ofSiOx having little or no hydrocarbon content is more hydrophilic than acoating of Si_(w)O_(x)C_(y)H_(z) as defined in the Definition Section.Generally speaking, the higher the C—H_(x) (e.g. CH, CH₂, or CH₃) moietycontent of the coating, either by weight, volume, or molarity, relativeto its silicon content, the more hydrophobic the coating.

A hydrophobic layer or coating can be very thin, having a thickness ofat least 4 nm, or at least 7 nm, or at least 10 nm, or at least 20 nm,or at least 30 nm, or at least 40 nm, or at least 50 nm, or at least 100nm, or at least 150 nm, or at least 200 nm, or at least 300 nm, or atleast 400 nm, or at least 500 nm, or at least 600 nm, or at least 700nm, or at least 800 nm, or at least 900 nm. The coating can be up to1000 nm, or at most 900 nm, or at most 800 nm, or at most 700 nm, or atmost 600 nm, or at most 500 nm, or at most 400 nm, or at most 300 nm, orat most 200 nm, or at most 100 nm, or at most 90 nm, or at most 80 nm,or at most 70 nm, or at most 60 nm, or at most 50 nm, or at most 40 nm,or at most 30 nm, or at most 20 nm, or at most 10 nm, or at most 5 nmthick. Specific thickness ranges composed of any one of the minimumthicknesses expressed above, plus any equal or greater one of themaximum thicknesses expressed above, are expressly contemplated.

One utility for such a hydrophobic layer or coating is to isolate athermoplastic tube wall, made for example of polyethylene terephthalate(PET), from blood collected within the tube. The hydrophobic layer orcoating can be applied on top of a hydrophilic SiO_(x) coating on theinternal surface of the tube. The SiO_(x) coating increases the barrierproperties of the thermoplastic tube and the hydrophobic layer orcoating changes the surface energy of blood contact surface with thetube wall. The hydrophobic layer or coating can be made by providing aprecursor selected from those identified in this specification. Forexample, the hydrophobic layer or coating precursor can comprisehexamethyldisiloxane (HMDSO) or octamethylcyclotetrasiloxane (OMCTS).

Another use for a hydrophobic layer or coating is to prepare a glasscell preparation tube. The tube has a wall defining a lumen, ahydrophobic layer or coating in the internal surface of the glass wall,and contains a citrate reagent. The hydrophobic layer or coating can bemade by providing a precursor selected from those identified elsewherein this specification. For another example, the hydrophobic layer orcoating precursor can comprise hexamethyldisiloxane (HMDSO) oroctamethylcyclotetrasiloxane (OMCTS). Another source material forhydrophobic layers is an alkyl trimethoxysilane of the formula:

R—Si(OCH₃)₃

in which R is a hydrogen atom or an organic substituent, for examplemethyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, vinyl,alkyne, epoxide, or others. Combinations of two or more of these arealso contemplated.

Combinations of acid or base catalysis and heating, using an alkyltrimethoxysilane precursor as described above, can condense theprecursor (removing ROH by-products) to form crosslinked polymers, whichcan optionally be further crosslinked via an alternative method. Onespecific example is by Shimojima et. al. J. Mater. Chem., 2007, 17,658-663.

A lubricity layer can be applied as a subsequent coating after applyingan SiO_(x) barrier coating to the interior surface 88 of the vessel 80to provide a lubricity layer, particularly if the lubricity layer orcoating is a liquid organosiloxane compound at the end of the coatingprocess.

Optionally, after the lubricity layer or coating is applied, it can bepost-cured after the PECVD process. Radiation curing approaches,including UV-initiated (free radial or cationic), electron-beam(E-beam), and thermal as described in Development Of NovelCycloaliphatic Siloxanes For Thermal And UV-Curable Applications (RubyChakraborty Dissertation, can 2008) be utilized.

Another approach for providing a lubricity layer or coating is to use asilicone demolding agent when injection-molding the thermoplastic vesselto be lubricated. For example, it is contemplated that any of thedemolding agents and latent monomers causing in-situ thermal lubricitylayer or coating formation during the molding process can be used. Or,the aforementioned monomers can be doped into traditional demoldingagents to accomplish the same result.

A lubricity layer, is particularly contemplated for the internal surfaceof a syringe barrel as further described below. A lubricated internalsurface of a syringe barrel can reduce the plunger sliding force neededto advance a plunger in the barrel during operation of a syringe, or thebreakout force to start a plunger moving after the prefilled syringeplunger has pushed away the intervening lubricant or adhered to thebarrel, for example due to decomposition of the lubricant between theplunger and the barrel. As explained elsewhere in this specification, alubricity layer or coating also can be applied to the interior surface88 of the vessel 80 to improve adhesion of a subsequent coating ofSiO_(x).

Thus, the coating 90 can comprise a layer or coating of SiO_(x) and alubricity layer or coating and/or hydrophobic layer, characterized asdefined in the Definition Section. The lubricity layer or coating and/orhydrophobic layer or coating of Si_(w)O_(x)C_(y)H_(z) can be depositedbetween the layer or coating of SiO_(x) and the interior surface of thevessel. Or, the layer or coating of SiO_(x) can be deposited between thelubricity layer or coating and/or hydrophobic layer or coating and theinterior surface of the vessel. Or, three or more layers, eitheralternating or graduated between these two coating compositions: (1) alayer or coating of SiO_(x) and (2) the lubricity layer or coatingand/or hydrophobic layer; can also be used. The layer or coating ofSiO_(x) can be deposited adjacent to the lubricity layer or coatingand/or hydrophobic layer or coating or remotely, with at least oneintervening layer or coating of another material. The layer or coatingof SiO_(x) can be deposited adjacent to the interior surface of thevessel. Or, the lubricity layer or coating and/or hydrophobic layer orcoating can be deposited adjacent to the interior surface of the vessel.

Another expedient contemplated here, for adjacent layers of SiO_(x) anda lubricity layer or coating and/or hydrophobic layer, is a gradedcomposite of Si_(w)O_(x)C_(y)H_(z), as defined in the DefinitionSection. A graded composite can be separate layers of a lubricity layeror coating and/or hydrophobic layer or coating and SiO_(x) with atransition or interface of intermediate composition between them, orseparate layers of a lubricity layer or coating and/or hydrophobic layeror coating and SiO_(x) with an intermediate distinct layer or coating ofintermediate composition between them, or a single layer or coating thatchanges continuously or in steps from a composition of a lubricity layeror coating and/or hydrophobic layer or coating to a composition morelike SiO_(x), going through the coating in a normal direction.

The grade in the graded composite can go in either direction. Forexample, the a lubricity layer or coating and/or hydrophobic layer orcoating can be applied directly to the substrate and graduate to acomposition further from the surface of SiO_(x). Or, the composition ofSiO_(x) can be applied directly to the substrate and graduate to acomposition further from the surface of a lubricity layer or coatingand/or hydrophobic layer. A graduated coating is particularlycontemplated if a coating of one composition is better for adhering tothe substrate than the other, in which case the better-adheringcomposition can, for example, be applied directly to the substrate. Itis contemplated that the more distant portions of the graded coating canbe less compatible with the substrate than the adjacent portions of thegraded coating, since at any point the coating is changing gradually inproperties, so adjacent portions at nearly the same depth of the coatinghave nearly identical composition, and more widely physically separatedportions at substantially different depths can have more diverseproperties. It is also contemplated that a coating portion that forms abetter barrier against transfer of material to or from the substrate canbe directly against the substrate, to prevent the more remote coatingportion that forms a poorer barrier from being contaminated with thematerial intended to be barred or impeded by the barrier.

The coating, instead of being graded, optionally can have sharptransitions between one layer or coating and the next, without asubstantial gradient of composition. Such coatings can be made, forexample, by providing the gases to produce a layer or coating as asteady state flow in a non-plasma state, then energizing the system witha brief plasma discharge to form a coating on the substrate. If asubsequent coating is to be applied, the gases for the previous coatingare cleared out and the gases for the next coating are applied in asteady-state fashion before energizing the plasma and again forming adistinct layer or coating on the surface of the substrate or itsoutermost previous coating, with little if any gradual transition at theinterface.

VII.A.1.a. Exemplary Vessels

VII.A.1.a. Referring to FIG. 1, more details of the vessel such as 80are shown. The illustrated vessel 80 can be generally tubular, having anopening 82 at one end of the vessel, opposed by a closed end 84. Thevessel 80 also has a wall 86 defining an interior surface 88. Oneexample of the vessel 80 is a medical sample tube, such as an evacuatedblood collection tube, as commonly is used by a phlebotomist forreceiving a venipuncture sample of a patient's blood for use in amedical laboratory.

VII.A.1.a. The vessel 80 can be made, for example, of thermoplasticmaterial. Some examples of suitable thermoplastic material arepolyethylene terephthalate or a polyolefin such as polypropylene or acyclic polyolefin copolymer.

VII.A.1.a. The vessel 80 can be made by any suitable method, such as byinjection molding, by blow molding, by machining, by fabrication fromtubing stock, or by other suitable means. PECVD can be used to form acoating on the internal surface of SiO_(x).

VII.A.1.a. If intended for use as an evacuated blood collection tube,the vessel 80 desirably can be strong enough to withstand asubstantially total internal vacuum substantially without deformationwhen exposed to an external pressure of 760 Torr or atmospheric pressureand other coating processing conditions. This property can be provided,in a thermoplastic vessel 80, by providing a vessel 80 made of suitablematerials having suitable dimensions and a glass transition temperaturehigher than the processing temperature of the coating process, forexample a cylindrical wall 86 having sufficient wall thickness for itsdiameter and material.

VII.A.1.a. Medical vessels or containers like sample collection tubesand syringes are relatively small and are injection molded withrelatively thick walls, which renders them able to be evacuated withoutbeing crushed by the ambient atmospheric pressure. They are thusstronger than carbonated soft drink bottles or other larger orthinner-walled plastic containers. Since sample collection tubesdesigned for use as evacuated vessels typically are constructed towithstand a full vacuum during storage, they can be used as vacuumchambers.

VII.A.1.a. Such adaptation of the vessels to be their own vacuumchambers might eliminate the need to place the vessels into a vacuumchamber for PECVD treatment, which typically is carried out at very lowpressure. The use of a vessel as its own vacuum chamber can result infaster processing time (since loading and unloading of the parts from aseparate vacuum chamber is not necessary) and can lead to simplifiedequipment configurations. Furthermore, a vessel holder is contemplated,for certain embodiments, that will hold the device (for alignment to gastubes and other apparatus), seal the device (so that the vacuum can becreated by attaching the vessel holder to a vacuum pump) and move thedevice between molding and subsequent processing steps.

VII.A.1.a. A vessel 80 used as an evacuated blood collection tube shouldbe able to withstand external atmospheric pressure, while internallyevacuated to a reduced pressure useful for the intended application,without a substantial volume of air or other atmospheric gas leakinginto the tube (as by bypassing the closure) or permeating through thewall 86 during its shelf life. If the as-molded vessel 80 cannot meetthis requirement, it can be processed by coating the interior surface 88with a barrier or other type of coating 90. It is desirable to treatand/or coat the interior surfaces of these devices (such as samplecollection tubes and syringe barrels) to impart various properties thatwill offer advantages over existing polymeric devices and/or to mimicexisting glass products. It is also desirable to measure variousproperties of the devices before and/or after treatment or coating.

Further exemplary vessels are the syringes described herein.

VII.A.1.b. Vessel Having Wall Coated With Hydrophobic Coating

VII.A.1.b. Another embodiment is a vessel having a wall provided with ahydrophobic layer or coating on its inside surface and containing anaqueous sodium citrate reagent. The hydrophobic layer or coating can bealso be applied on top of a hydrophilic SiO_(x) coating on the internalsurface of the vessel. The SiO_(x) coating increases the barrierproperties of the plastic vessel and the hydrophobic layer or coatingchanges the surface energy of the contact surface of the composition orcompound inside the vessel with the vessel wall.

VII.A.1.b. The wall is made of thermoplastic material having an internalsurface defining a lumen.

VII.A.1.b. A vessel according to the embodiment VII.A.1.b can have afirst layer or coating of SiO_(x) on the internal surface of the tube,applied as explained in this specification, to function as an oxygenbarrier and extend the shelf life of an evacuated blood collection tubemade of thermoplastic material. A second layer or coating of ahydrophobic layer, characterized as defined in the Definition Section,can then be applied over the barrier layer or coating on the internalsurface of the vessel to provide a hydrophobic surface. In a bloodcollection tube or syringe, the coating optionally is effective toreduce the platelet activation of blood plasma treated with a sodiumcitrate additive and exposed to the inner surface, compared to the sametype of wall uncoated.

VII.A.1.b. PECVD is used to form a hydrophobic layer or coating on theinternal surface. Unlike conventional citrate blood collection tubes, ablood collection tube having a hydrophobic layer as defined herein doesnot require a coating of baked on silicone on the vessel wall, as isconventionally applied to make the surface of the tube hydrophobic.

VII.A.1.b. Both layers can be applied using the same precursor, forexample HMDSO or OMCTS, and different PECVD reaction conditions.

VII.A.1.b. When preparing a blood collection tube or syringe, a sodiumcitrate anticoagulation reagent may then be placed within the tube andit is evacuated and sealed with a closure to produce an evacuated bloodcollection tube. The components and formulation of the reagent are knownto those skilled in the art. The aqueous sodium citrate reagent isdisposed in the lumen of the tube in an amount effective to inhibitcoagulation of blood introduced into the tube.

VII.A.1.c. SiO_(x) Barrier Coated Double Wall Plastic Vessel—COC, PET,SiO_(x) Layers

VII.A.1.c. Another embodiment is a vessel having a wall at leastpartially enclosing a lumen. The wall has an interior polymer layer orcoating enclosed by an exterior polymer layer. One of the polymer layersis a layer or coating at least 0.1 mm thick of a cyclic olefin copolymer(COC) resin defining a water vapor barrier. Another of the polymerlayers is a layer or coating at least 0.1 mm thick of a polyester resin.

VII.A.1.c. The wall includes an oxygen barrier layer or coating ofSiO_(x) having a thickness of from about 10 to about 500 angstroms.

VII.A.1.c. In an embodiment, the vessel 80 can be a double-walled vesselhaving an inner wall 408 and an outer wall 410, respectively made of thesame or different materials. One particular embodiment of this type canbe made with one wall molded from a cyclic olefin copolymer (COC) andthe other wall molded from a polyester such as polyethyleneterephthalate (PET), with an SiO_(x) coating as previously described onthe interior surface 412. As needed, a tie coating or layer or coatingcan be inserted between the inner and outer walls to promote adhesionbetween them. An advantage of this wall construction is that wallshaving different properties can be combined to form a composite havingthe respective properties of each wall.

VII.A.1.c. As one example, the inner wall 408 can be made of PET coatedon the interior surface 412 with an SiO_(x) barrier layer, and the outerwall 410 can be made of COC. PET coated with SiO_(x), as shown elsewherein this specification, is an excellent oxygen barrier, while COC is anexcellent barrier for water vapor, providing a low water vaportransition rate (WVTR). This composite vessel can have superior barrierproperties for both oxygen and water vapor. This construction iscontemplated, for example, for an evacuated medical sample collectiontube that contains an aqueous reagent as manufactured, and has asubstantial shelf life, so it should have a barrier preventing transferof water vapor outward or transfer of oxygen or other gases inwardthrough its composite wall during its shelf life.

VII.A.1.c. As another example, the inner wall 408 can be made of COCcoated on the interior surface 412 with an SiO_(x) barrier layer, andthe outer wall 410 can be made of PET. This construction iscontemplated, for example, for a prefilled syringe that contains anaqueous sterile fluid as manufactured. The SiO_(x) barrier will preventoxygen from entering the syringe through its wall. The COC inner wallwill prevent ingress or egress of other materials such as water, thuspreventing the water in the aqueous sterile fluid from leachingmaterials from the wall material into the syringe. The COC inner wall isalso contemplated to prevent water derived from the aqueous sterilefluid from passing out of the syringe (thus undesirably concentratingthe aqueous sterile fluid), and will prevent non-sterile water or otherfluids outside the syringe from entering through the syringe wall andcausing the contents to become non-sterile. The COC inner wall is alsocontemplated to be useful for decreasing the breaking force or frictionof the plunger against the inner wall of a syringe.

VII.A.1.d. Method of Making Double Wall Plastic Vessel—COC, PET, SiO_(x)Layers

VII.A.1.d. Another embodiment is a method of making a vessel having awall having an interior polymer layer or coating enclosed by an exteriorpolymer layer, one layer or coating made of COC and the other made ofpolyester. The vessel is made by a process including introducing COC andpolyester resin layers into an injection mold through concentricinjection nozzles.

VII.A.1.d. An optional additional step is applying an amorphous carboncoating to the vessel by PECVD, as an inside coating, an outsidecoating, or as an interlayer or coating coating located between thelayers.

VII.A.1.d. An optional additional step is applying an SiO_(x) barrierlayer or coating to the inside of the vessel wall, where SiO_(x) isdefined as before. Another optional additional step is post-treating theSiO_(x) layer or coating with a gaseous reactant or process gasconsisting essentially of oxygen and essentially free of a volatilesilicon compound.

VII.A.1.d. Optionally, the SiO_(x) coating can be formed at leastpartially from a silazane feed gas.

VII.A.1.d. The vessel 80 can be made from the inside out, for oneexample, by injection molding the inner wall in a first mold cavity,then removing the core and molded inner wall from the first mold cavityto a second, larger mold cavity, then injection molding the outer wallagainst the inner wall in the second mold cavity. Optionally, a tielayer or coating can be provided to the exterior surface of the moldedinner wall before over-molding the outer wall onto the tie layer.

VII.A.1.d. Or, the vessel 80 can be made from the outside in, for oneexample, by inserting a first core in the mold cavity, injection moldingthe outer wall in the mold cavity, then removing the first core from themolded first wall and inserting a second, smaller core, then injectionmolding the inner wall against the outer wall still residing in the moldcavity. Optionally, a tie layer or coating can be provided to theinterior surface of the molded outer wall before over-molding the innerwall onto the tie layer.

VII.A.1.d. Or, the vessel 80 can be made in a two shot mold. This can bedone, for one example, by injection molding material for the inner wallfrom an inner nozzle and the material for the outer wall from aconcentric outer nozzle. Optionally, a tie layer or coating can beprovided from a third, concentric nozzle disposed between the inner andouter nozzles. The nozzles can feed the respective wall materialssimultaneously. One useful expedient is to begin feeding the outer wallmaterial through the outer nozzle slightly before feeding the inner wallmaterial through the inner nozzle. If there is an intermediateconcentric nozzle, the order of flow can begin with the outer nozzle andcontinue in sequence from the intermediate nozzle and then from theinner nozzle. Or, the order of beginning feeding can start from theinside nozzle and work outward, in reverse order compared to thepreceding description.

VII.A.1.e. Vessel or Coating Made Of Glass

VII.A.1.e. Another embodiment is a vessel including a vessel, a barriercoating, and a closure. The vessel is generally tubular and made ofthermoplastic material. The vessel has a mouth and a lumen bounded atleast in part by a wall having an inner surface interfacing with thelumen. There is an at least essentially continuous barrier coating madeof glass on the inner surface of the wall. A closure covers the mouthand isolates the lumen of the vessel from ambient air.

VII.A.1.e. The vessel 80 can also be made, for example of glass of anytype used in medical or laboratory applications, such as soda-limeglass, borosilicate glass, or other glass formulations. Other vesselshaving any shape or size, made of any material, are also contemplatedfor use in the system 20. One function of coating a glass vessel can beto reduce the ingress of ions in the glass, either intentionally or asimpurities, for example sodium, calcium, or others, from the glass tothe contents of the vessel, such as a reagent or blood in an evacuatedblood collection tube. Another function of coating a glass vessel inwhole or in part, such as selectively at surfaces contacted in slidingrelation to other parts, is to provide lubricity to the coating, forexample to ease the insertion or removal of a stopper or passage of asliding element such as a piston in a syringe. Still another reason tocoat a glass vessel is to prevent a reagent or intended sample for thevessel, such as blood, from sticking to the wall of the vessel or anincrease in the rate of coagulation of the blood in contact with thewall of the vessel.

VII.A.1.e.i. A related embodiment is a vessel as described in theprevious paragraph, in which the barrier coating is made of soda limeglass, borosilicate glass, or another type of glass.

VII.A.2. Stoppers

VII.A.2. FIGS. 5-7 illustrate a vessel 268, which can be an evacuatedblood collection tube, having a closure 270 to isolate the lumen 274from the ambient environment. The closure 270 comprises ainterior-facing surface 272 exposed to the lumen 274 of the vessel 268and a wall-contacting surface 276 that is in contact with the innersurface 278 of the vessel wall 280. In the illustrated embodiment theclosure 270 is an assembly of a stopper 282 and a shield 284.

VII.A.2.a. Method of Applying Lubricity layer or coating to Stopper InVacuum Chamber

VII.A.2.a. Another embodiment is a method of applying a coating on anelastomeric stopper such as 282. The stopper 282, separate from thevessel 268, is placed in a substantially evacuated chamber. A reactionmixture is provided including plasma forming gas, i.e. an organosiliconcompound gas, optionally an oxidizing gas, and optionally a hydrocarbongas. Plasma is formed in the reaction mixture, which is contacted withthe stopper. A lubricity and/or hydrophobic layer, characterized asdefined in the Definition Section, is deposited on at least a portion ofthe stopper.

VII.A.2.a. In the illustrated embodiment, the wall-contacting surface276 of the closure 270 is coated with a lubricity layer or coating 286.

VII.A.2.a. In some embodiments, the lubricity and/or hydrophobic layer,characterized as defined in the Definition Section, is effective toreduce the transmission of one or more constituents of the stopper, suchas a metal ion constituent of the stopper, or of the vessel wall, intothe vessel lumen. Certain elastomeric compositions of the type usefulfor fabricating a stopper 282 contain trace amounts of one or more metalions. These ions sometimes should not be able to migrate into the lumen274 or come in substantial quantities into contact with the vesselcontents, particularly if the sample vessel 268 is to be used to collecta sample for trace metal analysis. It is contemplated for example thatcoatings containing relatively little organic content, i.e. where y andz of Si_(w)O_(x)C_(y)H_(z) as defined in the Definition Section are lowor zero, are particularly useful as a metal ion barrier in thisapplication. Regarding silica as a metal ion barrier see, for example,Anupama Mallikarjunan, Jasbir Juneja, Guangrong Yang, Shyam P. Murarka,and Toh-Ming Lu, The Effect of Interfacial Chemistry on Metal IonPenetration into Polymeric Films, Mat. Res. Soc. Symp. Proc., Vol. 734,pp. B9.60.1 to B9.60.6 (Materials Research Society, 2003); U.S. Pat.Nos. 5,578,103 and 6,200,658, and European Appl. EP0697378 A2, which areall incorporated here by reference. It is contemplated, however, thatsome organic content can be useful to provide a more elastic coating andto adhere the coating to the elastomeric surface of the stopper 282.

VII.A.2.a. In some embodiments, the lubricity and/or hydrophobic layer,characterized as defined in the Definition Section, can be a compositeof material having first and second layers, in which the first or innerlayer or coating 288 interfaces with the elastomeric stopper 282 and iseffective to reduce the transmission of one or more constituents of thestopper 282 into the vessel lumen. The second layer or coating 286 caninterface with the inner wall 280 of the vessel and is effective as alubricity layer or coating to reduce friction between the stopper 282and the inner wall 280 of the vessel when the stopper 282 is seated onor in the vessel 268. Such composites are described in connection withsyringe coatings elsewhere in this specification.

VII.A.2.a. Or, the first and second layers 288 and 286 are defined by acoating of graduated properties, in which the values of y and z definedin the Definition Section are greater in the first layer or coating thanin the second layer.

VII.A.2.a. The lubricity and/or hydrophobic layer or coating can beapplied, for example, by PECVD substantially as previously described.The lubricity and/or hydrophobic layer or coating can be, for example,between 0.5 and 5000 nm (5 to 50,000 Angstroms) thick, or between 1 and5000 nm thick, or between 5 and 5000 nm thick, or between 10 and 5000 nmthick, or between 20 and 5000 nm thick, or between 50 and 5000 nm thick,or between 100 and 5000 nm thick, or between 200 and 5000 nm thick, orbetween 500 and 5000 nm thick, or between 1000 and 5000 nm thick, orbetween 2000 and 5000 nm thick, or between 3000 and 5000 nm thick, orbetween 4000 and 10,000 nm thick.

VII.A.2.a. Certain advantages are contemplated for plasma coatedlubricity layers, versus the much thicker (one micron or greater)conventional spray applied silicone lubricants. Plasma coatings have amuch lower migratory potential to move into blood versus sprayed ormicron-coated silicones, both because the amount of plasma coatedmaterial is much less and because it can be more intimately applied tothe coated surface and better bonded in place.

VII.A.2.a. Nanocoatings, as applied by PECVD, are contemplated to offerlower resistance to sliding of an adjacent surface or flow of anadjacent fluid than micron coatings, as the plasma coating tends toprovide a smoother surface.

VII.A.2.a. Still another embodiment is a method of applying a coating ofa lubricity and/or hydrophobic layer or coating on an elastomericstopper. The stopper can be used, for example, to close the vesselpreviously described. The method includes several parts. A stopper isplaced in a substantially evacuated chamber. A reaction mixture isprovided comprising plasma forming gas, i.e. an organosilicon compoundgas, optionally an oxidizing gas, and optionally a hydrocarbon gas.Plasma is formed in the reaction mixture. The stopper is contacted withthe reaction mixture, depositing the coating of a lubricity and/orhydrophobic layer or coating on at least a portion of the stopper.

VII.A.2.a. In practicing this method, to obtain higher values of y and zas defined in the Definition Section, it is contemplated that thereaction mixture can comprise a hydrocarbon gas, as further describedabove and below. Optionally, the reaction mixture can contain oxygen, iflower values of y and z or higher values of x are contemplated. Or,particularly to reduce oxidation and increase the values of y and z, thereaction mixture can be essentially free of an oxidizing gas.

VII.A.2.a. In practicing this method to coat certain embodiments of thestopper such as the stopper 282, it is contemplated to be unnecessary toproject the reaction mixture into the concavities of the stopper. Forexample, the wall-contacting and interior facing surfaces 276 and 272 ofthe stopper 282 are essentially convex, and thus readily treated by abatch process in which a multiplicity of stoppers such as 282 can belocated and treated in a single substantially evacuated reactionchamber. It is further contemplated that in some embodiments thecoatings 286 and 288 do not need to present as formidable a barrier tooxygen or water as the barrier coating on the interior surface 280 ofthe vessel 268, as the material of the stopper 282 can serve thisfunction to a large degree.

VII.A.2.a. Many variations of the stopper and the stopper coatingprocess are contemplated. The stopper 282 can be contacted with theplasma. Or, the plasma can be formed upstream of the stopper 282,producing plasma product, and the plasma product can be contacted withthe stopper 282. The plasma can be formed by exciting the reactionmixture with electromagnetic energy and/or microwave energy.

VII.A.2.a. Variations of the reaction mixture are contemplated. Theplasma forming gas can include an inert gas, also referred to herein asa carrier gas. The inert gas can be, for example, argon, helium, xenon,neon, krypton, or any mixture of two or more of these. In particular,the inert gas can be neon, argon or helium. The organosilicon compoundgas can be, or include, HMDSO, OMCTS, any of the other organosiliconcompounds mentioned in this disclosure, or a combination of two or moreof these. The oxidizing gas can be oxygen or the other gases mentionedin this disclosure, or a combination of two or more of these. Thehydrocarbon gas can be, for example, methane, methanol, ethane,ethylene, ethanol, propane, propylene, propanol, acetylene, or acombination of two or more of these.

VII.A.2.b. Applying by PECVD a Coating of Group III or IV Element andCarbon on a Stopper

VII.A.2.b. Another embodiment is a method of applying a coating of acomposition including carbon and one or more elements of Groups III orIV on an elastomeric stopper. To carry out the method, a stopper islocated in a deposition chamber.

VII.A.2.b. A reaction mixture is provided in the deposition chamber,including a plasma forming gas with a gaseous source of a Group IIIelement, a Group IV element, or a combination of two or more of these.The reaction mixture optionally contains an oxidizing gas and optionallycontains a gaseous compound having one or more C—H bonds. Plasma isformed in the reaction mixture, and the stopper is contacted with thereaction mixture. A coating of a Group III element or compound, a GroupIV element or compound, or a combination of two or more of these isdeposited on at least a portion of the stopper.

VII.A.3. Stoppered Plastic Vessel Having Barrier Coating Effective ToProvide 95% Vacuum Retention for 24 Months

VII.A.3. Another embodiment is a vessel including a vessel, a barriercoating, and a closure. The vessel is generally tubular and made ofthermoplastic material. The vessel has a mouth and a lumen bounded atleast in part by a wall. The wall has an inner surface interfacing withthe lumen. An at least essentially continuous barrier coating is appliedon the inner surface of the wall. The barrier coating is effective toprovide a substantial shelf life. A closure is provided covering themouth of the vessel and isolating the lumen of the vessel from ambientair.

VII.A.3. Referring to FIGS. 5-7, a vessel 268 such as an evacuated bloodcollection tube or other vessel is shown.

VII.A.3. The vessel is, in this embodiment, a generally tubular vesselhaving an at least essentially continuous barrier coating and a closure.The vessel is made of thermoplastic material having a mouth and a lumenbounded at least in part by a wall having an inner surface interfacingwith the lumen. The barrier coating is deposited on the inner surface ofthe wall, and is effective to maintain at least 95%, or at least 90%, ofthe initial vacuum level of the vessel for a shelf life of at least 24months, optionally at least 30 months, optionally at least 36 months.The closure covers the mouth of the vessel and isolates the lumen of thevessel from ambient air.

VII.A.3. The closure, for example the closure 270 illustrated in theFigures or another type of closure, is provided to maintain a partialvacuum and/or to contain a sample and limit or prevent its exposure tooxygen or contaminants. FIGS. 5-7 are based on figures found in U.S.Pat. No. 6,602,206, but the present discovery is not limited to that orany other particular type of closure.

VII.A.3. The closure 270 comprises a interior-facing surface 272 exposedto the lumen 274 of the vessel 268 and a wall-contacting surface 276that is in contact with the inner surface 278 of the vessel wall 280. Inthe illustrated embodiment the closure 270 is an assembly of a stopper282 and a shield 284.

VII.A.3. In the illustrated embodiment, the stopper 282 defines thewall- contacting surface 276 and the inner surface 278, while the shieldis largely or entirely outside the stoppered vessel 268, retains andprovides a grip for the stopper 282, and shields a person removing theclosure 270 from being exposed to any contents expelled from the vessel268, such as due to a pressure difference inside and outside of thevessel 268 when the vessel 268 is opened and air rushes in or out toequalize the pressure difference.

VII.A.3. It is further contemplated that the coatings on the vessel wall280 and the wall contacting surface 276 of the stopper can becoordinated. The stopper can be coated with a lubricity silicone layer,and the vessel wall 280, made for example of PET or glass, can be coatedwith a harder SiO_(x) layer, or with an underlying SiO_(x) layer orcoating and a lubricity overcoat.

VII.B. Syringes

VII.B. The foregoing description has largely addressed applying abarrier coating to a tube with one permanently closed end, such as ablood collection tube or, more generally, a specimen receiving tube 80.The apparatus is not limited to such a device.

VII.B. Another example of a suitable vessel, shown in FIG. 20, is asyringe barrel 250 for a medical syringe 252. Such syringes 252 aresometimes supplied prefilled with saline solution, a pharmaceuticalpreparation, or the like for use in medical techniques. Pre-filledsyringes 252 are also contemplated to benefit from an SiO_(x) barrier orother type of coating on the interior surface 254 to keep the contentsof the prefilled syringe 252 out of contact with the plastic of thesyringe, for example of the syringe barrel 250 during storage. Thebarrier or other type of coating can be used to avoid leachingcomponents of the plastic into the contents of the barrel through theinterior surface 254.

VII.B. A syringe barrel 250 as molded commonly can be open at both theback end 256, to receive a plunger 258, and at the front end 260, toreceive a hypodermic needle, a nozzle, or tubing for dispensing thecontents of the syringe 252 or for receiving material into the syringe252. But the front end 260 can optionally be capped and the plunger 258optionally can be fitted in place before the prefilled syringe 252 isused, closing the barrel 250 at both ends. A cap 262 can be installedeither for the purpose of processing the syringe barrel 250 or assembledsyringe, or to remain in place during storage of the prefilled syringe252, up to the time the cap 262 is removed and (optionally) a hypodermicneedle or other delivery conduit is fitted on the front end 260 toprepare the syringe 252 for use.

Another example of a suitable vessel, shown in 24-26, is a syringeincluding a plunger, a syringe barrel, and a staked needle (a “stakedneedle syringe”). The needle is hollow with a typical size ranging from18-29 gauge. The syringe barrel has an interior surface slidablyreceiving the plunger. The staked needle may be affixed to the syringeduring the injection molding of the syringe or may be assembled to theformed syringe using an adhesive. A cover is placed over the stakedneedle to seal the syringe assembly. The syringe assembly must be sealedso that a vacuum can be maintained within the syringe to enable thePECVD coating process.

The needle of the staked needle syringe has an outside surface, adelivery outlet at one end, a base at the other end, and an internalpassage extending from the base to the delivery outlet. The barrel hasa, for example generally cylindrical, interior surface defining a lumen.The barrel also has a front passage molded around and in fluid-sealingcontact with the outside surface of the needle.

The syringe of any “staked needle” embodiment optionally can furtherinclude a cap configured to isolate the delivery outlet of the needlefrom ambient air.

The cap of any “staked needle” embodiment optionally can further includea lumen having an opening defined by a rim and sized to receive thedelivery outlet, and the rim can be seatable against an exterior portionof the barrel.

In the syringe of any “staked needle” embodiment, the barrel optionallycan further include a generally hemispheric interior surface portionadjacent to its front passage.

In the syringe of any “staked needle” embodiment, the base of the needleoptionally can be at least substantially flush with the hemisphericinterior surface portion of the barrel.

The syringe of any “staked needle” embodiment optionally can furtherinclude a PECVD-applied barrier coating on at least the hemisphericinterior surface portion of the barrel.

In the syringe of any “staked needle” embodiment, the barrier coatingoptionally can extend over at least a portion of the generallycylindrical interior surface portion of the barrel.

In the syringe of any “staked needle” embodiment, the barrier coatingoptionally can form a barrier between the base of the needle and thegenerally cylindrical interior surface portion of the barrel.

In the “staked needle” embodiment of FIG. 24, the cap 7126 is held inplace on the nose 71110 of the syringe 7120 by a conventional Luer lockarrangement. The tapered nose 71110 of the syringe mates with acorresponding tapered throat 71112 of the cap 7126, and the syringe hasa collar 71114 with an interior thread 71116 receiving the dogs 71118and 71120 of the cap 7126 to lock the tapers 71110 and 71112 together.The cap 7126 can be substantially rigid.

Referring now to FIGS. 25A, 25B, AND 25C, a variation on the syringebarrel 71122 and cap 71124 of the “staked needle” embodiment is shown.In this embodiment, the cap 71124 includes a flexible lip seal 7172 atits base to form a moisture-tight seal with the syringe barrel 71122.

Optionally in the “staked needle” embodiments of FIGS. 24 and 25, thecaps 7126 and 71124 can withstand vacuum during the PECVD coatingprocess. The caps 7126 and 71124 can be made of LDPE. Alternative rigidplastic materials can be used as well, for example polypropylene.Additional sealing elements can be provided as well.

In another option of the “staked needle” embodiment, illustrated in FIG.26, the cap 71126 is flexible, and is designed to seal around the topend of the syringe 7120. A deformable material—like a rubber or athermoplastic elastomer (TPE) can be used for the cap 71126. PreferredTPE materials include fluoroelastomers, and in particular, medical gradefluoroelastomers. Examples include VITON® and TECHNOFLON®. VITON® ispreferable in some embodiments. An example of a suitable rubber is EPDMrubber.

During molding, in certain “staked needle” embodiments (illustrated forexample in FIG. 26) a small amount of the cap material 71132 will bedrawn into the tip or delivery outlet 7134 of the needle 7122 to createa seal. The material 71132 should have a durometer such as to permit anappropriate amount of material to be drawn into the needle 7122, and tocause the material drawn into the needle 7122 to continue to adhere tothe cap 71126 when it is removed, unplugging the needle 7122 for use.

In other “staked needle” embodiments, the cap material 71132 can blockthe delivery outlet 7134 of the needle 7122 without being drawn into thedelivery outlet 7134. Suitable material selection to accomplish thedesired purposes is within the capabilities of a person of ordinaryskill in the art.

An additional seal can be created by coupling an undercut 71134 formedin the syringe barrel and projections 71138 in the interior of the cap71126, defining a coupling to retain the cap 71126. Alternative “stakedneedle” embodiments can include either one or both of the sealsdescribed above.

Optionally, with reference to FIGS. 25A, 25B, AND 25C, the cap 71124 canhave a base 7168 and a coupling 7170 configured for securing the cap7126 in a seated position on the barrel. Alternatively or in addition, aflexible lip seal 7172 can optionally be provided at the base 7168 ofthe cap 71124 for seating against the barrel 71122 when the cap 71124 issecured on the barrel 71122.

Optionally, referring now to FIG. 26, the delivery outlet 7134 of theneedle 7122 can be seated on the cap 71126 when the cap 7126 is securedon the barrel. This expedient is useful for sealing the delivery outlet7134 against the ingress or egress of air or other fluids, when that isdesired.

Optionally, in the “staked needle” embodiment the coupling 7170 caninclude a detent or groove 7174 on one of the barrel 71122 and the cap71124 and a projection or rib 76 on the other of the barrel 71122 andthe cap 71124, the projection 7176 being adapted to mate with the detent7174 when the cap 7126 is in its seated position on the barrel. In onecontemplated embodiment, a detent 7174 can be on the barrel and aprojection 7176 can be on the cap 7126. In another contemplatedembodiment, a detent 7174 can be on the cap 7126 and a projection 7176can be on the barrel. In yet another contemplated embodiment, a firstdetent 7174 can be on the barrel and a first projection 7176 mating withthe detent 7174 can be on the cap 7126, while a second detent 7175 canbe on the cap 7126 and the mating second projection 7177 can be on thebarrel. A detent 7174 can be molded in the syringe barrel as an undercutby incorporating side draws such as 7192 and 7194 in the mold. Thedetents 7174 mate with the complementary projections 7176 to assemble(snap) the cap 7126 onto the syringe 7120. In this respect the cap 7126is desirably flexible enough to allow sufficient deformation for asnapping engagement of the detents 7174 and projections 7176.

The caps in the “staked needle” embodiment such as 7126, 71124, and71126 can be injection molded or otherwise formed, for example fromthermoplastic material. Several examples of suitable thermoplasticmaterial are a polyolefin, for example a cyclic olefin polymer (COP), acyclic olefin copolymer (COC), polypropylene, or polyethylene. The cap7126 can contain or be made of a thermoplastic elastomer (TPE) or otherelastomeric material. The cap 7126 can also be made of polyethyleneterephthalate (PET), polycarbonate resin, or any other suitablematerial. Optionally, a material for the cap 7126 can be selected thatcan withstand vacuum and maintain sterility within the syringe 7120.

Typically, when the syringe barrel is coated, the PECVD coating methodsdescribed herein are performed such that the coated substrate surface ispart or all of the inner surface of the barrel, the gas for the PECVDreaction fills the interior lumen of the barrel, and the plasma isgenerated within part or all of the interior lumen of the barrel.

VII.B.1.a. Syringe Having Barrel Coated with Lubricity Layer

VII.B.1.a. A syringe having a lubricity layer of the type can be made bythe following process.

VII.B.1.a. A precursor is provided as defined above.

VII.B.1.a. The precursor is applied to a substrate under conditionseffective to form a coating. The coating is polymerized or crosslinked,or both, to form a lubricated surface having a lower plunger slidingforce or breakout force than the untreated substrate.

VII.B.1.a. Respecting any of the Embodiments VII and sub-parts,optionally the applying step is carried out by vaporizing the precursorand providing it in the vicinity of the substrate.

VII.B.1.a. A plasma, is formed in the vicinity of the substrate.Optionally, the precursor is provided in the substantial absence ofnitrogen. Optionally, the precursor is provided at less than 1 Torrabsolute pressure. Optionally, the precursor is provided to the vicinityof a plasma emission. Optionally, the precursor its reaction product isapplied to the substrate at an average thickness of 1 to 5000 nm, or 10to 1000 nm, or 10 to 500 nm, or 10 to 200 nm, or 20 to 100 nm, or 30 to1000 nm, or 30 to 500 nm, or 30 to 1000 nm, or 20 to 100 nm, or 80 to150 nm thick. Optionally, the substrate comprises glass. Optionally, thesubstrate comprises a polymer, optionally a polycarbonate polymer,optionally an olefin polymer, optionally a cyclic olefin copolymer,optionally a polypropylene polymer, optionally a polyester polymer,optionally a polyethylene terephthalate polymer. COC is particularlyconsidered for syringes and syringe barrels.

VII.B.1.a. Optionally, the plasma is generated by energizing the gaseousreactant containing the precursor with electrodes powered, for example,at a RF frequency as defined above, for example a frequency of from 10kHz to less than 300 MHz, optionally from 1 to 50 MHz, even optionallyfrom 10 to 15 MHz, optionally a frequency of 13.56 MHz.

VII.B.1.a. Optionally, the plasma is generated by energizing the gaseousreactant containing the precursor with electrodes supplied with anelectric power of from 0.1 to 25 W, optionally from 1 to 22 W,optionally from 3 to 17 W, even optionally from 5 to 14 W, optionallyfrom 7 to 11 W, optionally 8 W. The ratio of the electrode power to theplasma volume can be less than 10 W/ml, optionally is from 6 W/ml to 0.1W/ml, optionally is from 5 W/ml to 0.1 W/ml, optionally is from 4 W/mlto 0.1 W/ml, optionally is from 2 W/ml to 0.2 W/ml. Low power levels arebelieved by the inventors to be most advantageous (e.g. power levels offrom 2 to 3.5 W and the power levels given in the Examples) to prepare alubricity coating. These power levels are suitable for applyinglubricity layers to syringes and sample tubes and vessels of similargeometry having a void volume of 1 to 3 mL in which PECVD plasma isgenerated. It is contemplated that for larger or smaller objects thepower applied should be increased or reduced accordingly to scale theprocess to the size of the substrate.

VII.B.1.a. Another embodiment is a lubricity coating of the presentinvention on the inner wall of a syringe barrel. The coating is producedfrom a PECVD process using the following materials and conditions. Acyclic precursor is optionally employed, selected from a monocyclicsiloxane, a polycyclic siloxane, or a combination of two or more ofthese, as defined elsewhere in this specification for lubricity layers.One example of a suitable cyclic precursor comprisesoctamethylcyclotetrasiloxane (OMCTS), optionally mixed with otherprecursor materials in any proportion. Optionally, the cyclic precursorconsists essentially of octamethycyclotetrasiloxane (OMCTS), meaningthat other precursors can be present in amounts which do not change thebasic and novel properties of the resulting lubricity layer, i.e. itsreduction of the plunger sliding force or breakout force of the coatedsurface.

VII.B.1.a. A sufficient plasma generation power input, for example anypower level successfully used in one or more working examples of thisspecification or described in the specification, is provided to inducecoating formation.

VII.B.1.a. The materials and conditions employed are effective to reducethe syringe plunger sliding force or breakout force moving through thesyringe barrel at least 25 percent, alternatively at least 45 percent,alternatively at least 60 percent, alternatively greater than 60percent, relative to an uncoated syringe barrel. Ranges of plungersliding force or breakout force reduction of from 20 to 95 percent,alternatively from 30 to 80 percent, alternatively from 40 to 75percent, alternatively from 60 to 70 percent, are contemplated.

VII.B.1.a. Another embodiment is a vessel having a hydrophobic layer,characterized as defined in the Definition Section, on the inside wall.The coating is made as explained for the lubricant coating of similarcomposition, but under conditions effective to form a hydrophobicsurface having a higher contact angle than the untreated substrate.

VII.B.1.a. Respecting any of the Embodiments VII.A.1.a.ii, optionallythe substrate comprises glass or a polymer. The glass optionally isborosilicate glass. The polymer is optionally a polycarbonate polymer,optionally an olefin polymer, optionally a cyclic olefin copolymer,optionally a polypropylene polymer, optionally a polyester polymer,optionally a polyethylene terephthalate polymer.

VII.B.1.a. Another embodiment is a syringe including a plunger, asyringe barrel, and a lubricity layer. The syringe barrel includes aninterior surface receiving the plunger for sliding. The lubricity layeror coating is disposed on part or all of the interior surface of thesyringe barrel. The lubricity layer or coating optionally can be lessthan 1000 nm thick and effective to reduce the breakout force or theplunger sliding force necessary to move the plunger within the barrel.Reducing the plunger sliding force is alternatively expressed asreducing the coefficient of sliding friction of the plunger within thebarrel or reducing the plunger force; these terms are regarded as havingthe same meaning in this specification.

VII.B.1.a. The syringe 544 comprises a plunger 546 and a syringe barrel548. The syringe barrel 548 has an interior surface 552 receiving theplunger for sliding 546. The interior surface 552 of the syringe barrel548 further comprises a lubricity layer or coating 554. The lubricitylayer or coating is less than 1000 nm thick, optionally less than 500 nmthick, optionally less than 200 nm thick, optionally less than 100 nmthick, optionally less than 50 nm thick, and is effective to reduce thebreakout force necessary to overcome adhesion of the plunger afterstorage or the plunger sliding force necessary to move the plungerwithin the barrel after it has broken away. The lubricity layer orcoating is characterized by having a plunger sliding force or breakoutforce lower than that of the uncoated surface.

VII.B.1.a. Any of the above precursors of any type can be used alone orin combinations of two or more of them to provide a lubricity layer.

VII.B.1.a. In addition to utilizing vacuum processes, low temperatureatmospheric (non-vacuum) plasma processes can also be utilized to inducemolecular ionization and deposition through precursor monomer vapordelivery optionally in a non-oxidizing atmosphere such as helium orargon. Separately, thermal CVD can be considered via flash thermolysisdeposition.

VII.B.1.a. The approaches above are similar to vacuum PECVD in that thesurface coating and crosslinking mechanisms can occur simultaneously.

VII.B.1.a. Yet another expedient contemplated for any coating orcoatings described here is a coating that is not uniformly applied overthe entire interior 88 of a vessel. For example, a different oradditional coating can be applied selectively to the cylindrical portionof the vessel interior, compared to the hemispherical portion of thevessel interior at its closed end 84, or vice versa. This expedient isparticularly contemplated for a syringe barrel or a sample collectiontube as described below, in which a lubricity layer or coating might beprovided on part or all of the cylindrical portion of the barrel, wherethe plunger or piston or closure slides, and not elsewhere.

VII.B.1.a. Optionally, the precursor can be provided in the presence,substantial absence, or absence of nitrogen. In one contemplatedembodiment, the precursor alone is delivered to the substrate andsubjected to PECVD to apply and cure the coating.

VII.B.1.a. Optionally, the precursor can be provided at less than 1 Torrabsolute pressure.

VII.B.1.a. Optionally, the precursor can be provided to the vicinity ofa plasma emission.

VII.B.1.a. In any of the above embodiments, the substrate can compriseglass, or a polymer, for example one or more of a polycarbonate polymer,an olefin polymer (for example a cyclic olefin copolymer or apolypropylene polymer), or a polyester polymer (for example, apolyethylene terephthalate polymer).

VII.B.1.a. In any of the above embodiments, the plasma is generated byenergizing the gaseous reactant containing the precursor with electrodespowered at a RF frequency as defined in this description.

VII.B.1.a. In any of the above embodiments, the plasma is generated byenergizing the gaseous reactant containing the precursor with electrodessupplied with sufficient electric power to generate a lubricity layer.Optionally, the plasma is generated by energizing the gaseous reactantcontaining the precursor with electrodes supplied with an electric powerof from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 3 to 17W, even optionally from 5 to 14 W, optionally from 7 to 11 W, optionally8 W. The ratio of the electrode power to the plasma volume can be lessthan 10 W/ml, optionally is from 6 W/ml to 0.1 W/ml, optionally is from5 W/ml to 0.1 W/ml, optionally is from 4 W/ml to 0.1 W/ml, optionallyfrom 2 W/ml to 0.2 W/ml. Low power levels are believed by the inventorsto be most advantageous (e.g. power levels of from 2 to 3.5 W and thepower levels given in the Examples) to prepare a lubricity coating.These power levels are suitable for applying lubricity layers tosyringes and sample tubes and vessels of similar geometry having a voidvolume of 1 to 3 mL in which PECVD plasma is generated. It iscontemplated that for larger or smaller objects the power applied shouldbe increased or reduced accordingly to scale the process to the size ofthe substrate.

VII.B.1.a. The coating can be cured, as by polymerizing or crosslinkingthe coating, or both, to form a lubricated surface having a lowerplunger sliding force or breakout force than the untreated substrate.Curing can occur during the application process such as PECVD, or can becarried out or at least completed by separate processing.

VII.B.1.a. Although plasma deposition has been used herein todemonstrate the coating characteristics, alternate deposition methodscan be used as long as the chemical composition of the starting materialis preserved as much as possible while still depositing a solid filmthat is adhered to the base substrate.

VII.B.1.a. For example, the coating material can be applied onto thesyringe barrel (from the liquid state) by spraying the coating ordipping the substrate into the coating, where the coating is either theneat precursor a solvent-diluted precursor (allowing the mechanicaldeposition of a thinner coating). The coating optionally can becrosslinked using thermal energy, UV energy, electron beam energy,plasma energy, or any combination of these.

VII.B.1.a. Application of a silicone precursor as described above onto asurface followed by a separate curing step is also contemplated. Theconditions of application and curing can be analogous to those used forthe atmospheric plasma curing of pre-coated polyfluoroalkyl ethers, aprocess practiced under the trademark TriboGlide®. More details of thisprocess can be found at http://www.triboglide.com/process.htm.

VII.B.1.a. In such a process, the area of the part to be coated canoptionally be pre-treated with an atmospheric plasma. This pretreatmentcleans and activates the surface so that it is receptive to thelubricant that is sprayed in the next step.

VII.B.1.a. The lubrication fluid, in this case one of the aboveprecursors or a polymerized precursor, is then sprayed on to the surfaceto be treated. For example, IVEK precision dispensing technology can beused to accurately atomize the fluid and create a uniform coating.

VII.B.1.a. The coating is then bonded or crosslinked to the part, againusing an atmospheric plasma field. This both immobilizes the coating andimproves the lubricant's performance.

VII.B.1.a. Optionally, the atmospheric plasma can be generated fromambient air in the vessel, in which case no gas feed and no vacuumdrawing equipment is needed. Optionally, however, the vessel is at leastsubstantially closed while plasma is generated, to minimize the powerrequirement and prevent contact of the plasma with surfaces or materialsoutside the vessel.

VII.B.1.a.i. Lubricity layer: SiO_(x) Barrier, Lubricity Layer, SurfaceTreatment Surface treatment

VII.B.1.a.i. Another embodiment is a syringe comprising a barreldefining a lumen and having an interior surface slidably receiving aplunger, i.e. receiving a plunger for sliding contact to the interiorsurface.

VII.B.1.a.i. The syringe barrel is made of thermoplastic base material.

VII.B.1.a.i. Optionally, the interior surface of the barrel is coatedwith an SiO_(x) barrier layer or coating as described elsewhere in thisspecification.

VII.B.1.a.i. A lubricity layer or coating is applied to part or all thebarrel interior surface, the plunger, or both, or to the previouslyapplied SiO_(x) barrier layer. The lubricity layer or coating can beprovided, applied, and cured as set out in embodiment VII.B.1.a orelsewhere in this specification.

VII.B.1.a.i. For example, the lubricity layer or coating can be applied,in any embodiment, by PECVD. The lubricity layer or coating is depositedfrom an organosilicon precursor, and is less than 1000 nm thick.

VII.B.1.a.i. A surface treatment is carried out on the lubricity layeror coating in an amount effective to reduce the leaching or extractablesof the lubricity layer, the thermoplastic base material, or both. Thetreated surface can thus act as a solute retainer. This surfacetreatment can result in a skin coating, e.g. a skin coating which is atleast 1 nm thick and less than 100 nm thick, or less than 50 nm thick,or less than 40 nm thick, or less than 30 nm thick, or less than 20 nmthick, or less than 10 nm thick, or less than 5 nm thick, or less than 3nm thick, or less than 2 nm thick, or less than 1 nm thick, or less than0.5 nm thick.

VII.B.1.a.i. As used herein, “leaching” refers to material transferredout of a substrate, such as a vessel wall, into the contents of avessel, for example a syringe. Commonly, leachables are measured bystoring the vessel filled with intended contents, then analyzing thecontents to determine what material leached from the vessel wall intothe intended contents. “Extraction” refers to material removed from asubstrate by introducing a solvent or dispersion medium other than theintended contents of the vessel, to determine what material can beremoved from the substrate into the extraction medium under theconditions of the test.

VII.B.1.a.i. The surface treatment resulting in a solute retaineroptionally can be a SiO_(x) layer or coating as previously defined inthis specification or a hydrophobic layer, characterized as defined inthe Definition Section. In one embodiment, the surface treatment can beapplied by PECVD deposit of SiO_(x) or a hydrophobic layer. Optionally,the surface treatment can be applied using higher power or strongeroxidation conditions than used for creating the lubricity layer, orboth, thus providing a harder, thinner, continuous solute retainer 539.Surface treatment can be less than 100 nm deep, optionally less than 50nm deep, optionally less than 40 nm deep, optionally less than 30 nmdeep, optionally less than 20 nm deep, optionally less than 10 nm deep,optionally less than 5 nm deep, optionally less than 3 nm deep,optionally less than 1 nm deep, optionally less than 0.5 nm deep,optionally between 0.1 and 50 nm deep in the lubricity layer.

VII.B.1.a.i. The solute retainer is contemplated to provide low soluteleaching performance to the underlying lubricity and other layers,including the substrate, as required. This retainer would only need tobe a solute retainer to large solute molecules and oligomers (forexample siloxane monomers such as HMDSO, OMCTS, their fragments andmobile oligomers derived from lubricants, for example a “leachablesretainer”) and not a gas (O₂/N₂/CO₂/water vapor) barrier layer. A soluteretainer can, however, also be a gas barrier (e.g. the SiO_(x) coatingaccording to present invention. One can create a good leachable retainerwithout gas barrier performance, either by vacuum or atmospheric-basedPECVD processes. It is desirable that the “leachables barrier” will besufficiently thin that, upon syringe plunger movement, the plunger willreadily penetrate the “solute retainer” exposing the sliding plungernipple to the lubricity layer or coating immediately below to form alubricated surface having a lower plunger sliding force or breakoutforce than the untreated substrate.

VII.B.1.a.i. In another embodiment, the surface treatment can beperformed by oxidizing the surface of a previously applied lubricitylayer, as by exposing the surface to oxygen in a plasma environment. Theplasma environment described in this specification for forming SiO_(x)coatings can be used. Or, atmospheric plasma conditions can be employedin an oxygen-rich environment.

VII.B.1.a.i. The lubricity layer or coating and solute retainer, howeverformed, optionally can be cured at the same time. In another embodiment,the lubricity layer or coating can be at least partially cured,optionally fully cured, after which the surface treatment can beprovided, applied, and the solute retainer can be cured.

VII.B.1.a.i. The lubricity layer or coating and solute retainer arecomposed, and present in relative amounts, effective to provide abreakout force, plunger sliding force, or both that is less than thecorresponding force required in the absence of the lubricity layer orcoating and surface treatment. In other words, the thickness andcomposition of the solute retainer are such as to reduce the leaching ofmaterial from the lubricity layer or coating into the contents of thesyringe, while allowing the underlying lubricity layer or coating tolubricate the plunger. It is contemplated that the solute retainer willbreak away easily and be thin enough that the lubricity layer or coatingwill still function to lubricate the plunger when it is moved.

VII.B.1.a.i. In one contemplated embodiment, the lubricity and surfacetreatments can be applied on the barrel interior surface. In anothercontemplated embodiment, the lubricity and surface treatments can beapplied on the plunger. In still another contemplated embodiment, thelubricity and surface treatments can be applied both on the barrelinterior surface and on the plunger. In any of these embodiments, theoptional SiO_(x) barrier layer or coating on the interior of the syringebarrel can either be present or absent.

VII.B.1.a.i. One embodiment contemplated is a plural-layer, e.g. a3-layer, configuration applied to the inside surface of a syringebarrel. Layer or coating 1 can be an SiO_(x) gas barrier made by PECVDof HMDSO, OMCTS, or both, in an oxidizing atmosphere. Such an atmospherecan be provided, for example, by feeding HMDSO and oxygen gas to a PECVDcoating apparatus as described in this specification. Layer or coating 2can be a lubricity layer or coating using OMCTS applied in anon-oxidizing atmosphere. Such a non-oxidizing atmosphere can beprovided, for example, by feeding OMCTS to a PECVD coating apparatus asdescribed in this specification, optionally in the substantial orcomplete absence of oxygen. A subsequent solute retainer can be formedby a treatment forming a thin skin layer or coating of SiO_(x) or ahydrophobic layer or coating as a solute retainer using higher power andoxygen using OMCTS and/or HMDSO.

VII.B.1.a.i. Certain of these plural-layer or coating coatings arecontemplated to have one or more of the following optional advantages,at least to some degree. They can address the reported difficulty ofhandling silicone, since the solute retainer can confine the interiorsilicone and prevent if from migrating into the contents of the syringeor elsewhere, resulting in fewer silicone particles in the deliverablecontents of the syringe and less opportunity for interaction between thelubricity layer or coating and the contents of the syringe. They canalso address the issue of migration of the lubricity layer or coatingaway from the point of lubrication, improving the lubricity of theinterface between the syringe barrel and the plunger. For example, thebreak-free force can be reduced and the drag on the moving plunger canbe reduced, or optionally both.

VII.B.1.a.i. It is contemplated that when the solute retainer is broken,the solute retainer will continue to adhere to the lubricity layer orcoating and the syringe barrel, which can inhibit any particles frombeing entrained in the deliverable contents of the syringe.

VII.B.1.a.i. Certain of these coatings will also provide manufacturingadvantages, particularly if the barrier coating, lubricity layer orcoating and surface treatment are applied in the same apparatus, forexample the illustrated PECVD apparatus. Optionally, the SiO_(x) barriercoating, lubricity layer, and surface treatment can all be applied inone PECVD apparatus, thus greatly reducing the amount of handlingnecessary.

Further advantages can be obtained by forming the barrier coating,lubricity layer, and solute retainer using the same precursors andvarying the process. For example, an SiO_(x) gas barrier layer orcoating can be applied using an OMCTS precursor under high power/high 02conditions, followed by applying a lubricity layer or coating appliedusing an OMCTS precursor under low power and/or in the substantial orcomplete absence of oxygen, finishing with a surface treatment using anOMCTS precursor under intermediate power and oxygen.

VII.B.2. Plungers

VII.B.2.a. With Barrier Coated Piston Front Face

VII.B.2.a. Another embodiment is a plunger for a syringe, including apiston and a push rod. The piston has a front face, a generallycylindrical side face, and a back portion, the side face beingconfigured to movably seat within a syringe barrel. The front face has abarrier coating. The push rod engages the back portion and is configuredfor advancing the piston in a syringe barrel.

VII.B.2.b. With Lubricity Layer or Coating Interfacing with Side Face

VII.B.2.b. Yet another embodiment is a plunger for a syringe, includinga piston, a lubricity layer, and a push rod. The piston has a frontface, a generally cylindrical side face, and a back portion. The sideface is configured to movably seat within a syringe barrel. Thelubricity layer or coating interfaces with the side face. The push rodengages the back portion of the piston and is configured for advancingthe piston in a syringe barrel.

VII.B.3.a Two Piece Syringe and Luer Fitting

VII.B.3.a Another embodiment is a syringe including a plunger, a syringebarrel, and a Luer fitting. The syringe includes a barrel having aninterior surface receiving the plunger for sliding. The Luer fittingincludes a Luer taper having an internal passage defined by an internalsurface. The Luer fitting is formed as a separate piece from the syringebarrel and joined to the syringe barrel by a coupling. The internalpassage of the Luer taper optionally has a barrier coating of SiOx.

VII.B.3.b Staked Needle Syringe

VII.B.3.b Another embodiment is a syringe including a plunger, a syringebarrel, and a staked needle (a “staked needle syringe”). The needle ishollow with a typical size ranging from 18-29 gauge. The syringe barrelhas an interior surface slidably receiving the plunger. The stakedneedle may be affixed to the syringe during the injection molding of thesyringe or may be assembled to the formed syringe using an adhesive. Acover is placed over the staked needle to seal the syringe assembly. Thesyringe assembly must be sealed so that a vacuum can be maintainedwithin the syringe to enable the PECVD coating process.

VII.B.4. Lubricity layer or Coating in GeneralVII.B.4.a. Product By Process and Lubricity

VII.B.4.a. Still another embodiment is a lubricity layer. This coatingcan be of the type made by the process for preparing a lubricity coatingas described herein.

VII.B.4.a. Any of the precursors for lubricity coatings mentionedelsewhere in this specification can be used, alone or in combination.The precursor is applied to a substrate under conditions effective toform a coating. The coating is polymerized or crosslinked, or both, toform a lubricated surface having a lower plunger sliding force orbreakout force than the untreated substrate.

VII.B.4.a. Another embodiment is a method of applying a lubricity layer.An organosilicon precursor is applied to a substrate under conditionseffective to form a coating. The coating is polymerized or crosslinked,or both, to form a lubricated surface having a lower plunger slidingforce or breakout force than the untreated substrate.

VII.B.4.b. Product by Process and Analytical Properties

VII.B.4.b. Even another aspect of the invention is a lubricity layer orcoating deposited by PECVD from a feed gas comprising an organometallicprecursor, optionally an organosilicon precursor, optionally a linearsiloxane, a linear silazane, a monocyclic siloxane, a monocyclicsilazane, a polycyclic siloxane, a polycyclic silazane, or anycombination of two or more of these. The coating can have a densitybetween 1.25 and 1.65 g/cm³ optionally between 1.35 and 1.55 g/cm³,optionally between 1.4 and 1.5 g/cm³, optionally between 1.44 and 1.48g/cm³ as determined by X-ray reflectivity (XRR).

VII.B.4.b. Still another aspect of the invention is a lubricity layer orcoating deposited by PECVD from a feed gas comprising an organometallicprecursor, optionally an organosilicon precursor, optionally a linearsiloxane, a linear silazane, a monocyclic siloxane, a monocyclicsilazane, a polycyclic siloxane, a polycyclic silazane, or anycombination of two or more of these. The coating has as an outgascomponent one or more oligomers containing repeating —(Me)₂SiO—moieties, as determined by gas chromatography/mass spectrometry.Optionally, the coating meets the limitations of any of embodimentsVII.B.4.a. Optionally, the coating outgas component as determined by gaschromatography/mass spectrometry is substantially free oftrimethylsilanol.

VII.B.4.b. Optionally, the coating outgas component can be at least 10ng/test of oligomers containing repeating —(Me)₂SiO— moieties, asdetermined by gas chromatography/mass spectrometry using the followingtest conditions:

-   -   GC Column: 30m×0.25 mm DB-5MS (J&W Scientific), 0.25 μm film        thickness    -   Flow rate: 1.0 ml/min, constant flow mode    -   Detector: Mass Selective Detector (MSD)    -   Injection Mode: Split injection (10:1 split ratio)    -   Outgassing Conditions: 1½″ (37 mm) Chamber, purge for three hour        at 85° C., flow 60 ml/min    -   Oven temperature: 40° C. (5 min.) to 300° C. at 10° C./min.;        hold for 5 min. at 300° C.

VII.B.4.b. Optionally, the outgas component can include at least 20ng/test of oligomers containing repeating —(Me)₂SiO— moieties.

VII.B.4.b. Optionally, the feed gas comprises a monocyclic siloxane, amonocyclic silazane, a polycyclic siloxane, a polycyclic silazane, orany combination of two or more of these, for example a monocyclicsiloxane, a monocyclic silazane, or any combination of two or more ofthese, for example octamethylcyclotetrasiloxane.

VII.B.4.b. The lubricity layer or coating of any embodiment can have anaverage thickness measured by transmission electron microscopy (TEM) offrom 1 to 5000 nm, or 10 to 1000 nm, or 10 to 200 nm, or 20 to 100 nm,or 30 to 1000 nm, or 30 to 500 nm thick. Preferred ranges are from 30 to1000 nm and from 20 to 100 nm, and a particularly preferred range isfrom 80 to 150 nm. The absolute thickness of the coating at singlemeasurement points can be higher or lower than the range limits of theaverage thickness. However, it typically varies within the thicknessranges given for the average thickness.

VII.B.4.b. Another aspect of the invention is a lubricity layer orcoating deposited by PECVD from a feed gas comprising a monocyclicsiloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclicsilazane, or any combination of two or more of these. The coating has anatomic concentration of carbon, normalized to 100% of carbon, oxygen,and silicon, as determined by X-ray photoelectron spectroscopy (XPS),greater than the atomic concentration of carbon in the atomic formulafor the feed gas. Optionally, the coating meets the limitations ofembodiments VII.B.4.a or VII.B.4.b.A.

VII.B.4.b. Optionally, the atomic concentration of carbon increases byfrom 1 to 80 atomic percent (as calculated and based on the XPSconditions in Example 15 of EP 2 251 455), alternatively from 10 to 70atomic percent, alternatively from 20 to 60 atomic percent,alternatively from 30 to 50 atomic percent, alternatively from 35 to 45atomic percent, alternatively from 37 to 41 atomic percent in relationto the atomic concentration of carbon in the organosilicon precursorwhen a lubricity coating is made.

VII.B.4.b. An additional aspect of the invention is a lubricity layer orcoating deposited by PECVD from a feed gas comprising a monocyclicsiloxane, a monocyclic silazane, a polycyclic siloxane, a polycyclicsilazane, or any combination of two or more of these. The coating has anatomic concentration of silicon, normalized to 100% of carbon, oxygen,and silicon, as determined by X-ray photoelectron spectroscopy (XPS),less than the atomic concentration of silicon in the atomic formula forthe feed gas. See Example 15 of EP 2 251 455.

VII.B.4.b. Optionally, the atomic concentration of silicon decreases byfrom 1 to 80 atomic percent (as calculated and based on the XPSconditions in Example 15 of EP 2251 455), alternatively from 10 to 70atomic percent, alternatively from 20 to 60 atomic percent,alternatively from 30 to 55 atomic percent, alternatively from 40 to 50atomic percent, alternatively from 42 to 46 atomic percent.

VII.B.4.b. Lubricity layers having combinations of any two or moreproperties recited in Section VII.B.4 are also expressly contemplated.

VII.C. Vessels Generally

VII.C. A coated vessel or container as described herein and/or preparedaccording to a method described herein can be used for reception and/orstorage and/or delivery of a compound or composition. The compound orcomposition can be sensitive, for example air-sensitive,oxygen-sensitive, sensitive to humidity and/or sensitive to mechanicalinfluences. It can be a biologically active compound or composition, forexample a medicament like insulin or a composition comprising insulin.In another aspect, it can be a biological fluid, optionally a bodilyfluid, for example blood or a blood fraction. In certain aspects of thepresent invention, the compound or composition is a product to beadministrated to a subject in need thereof, for example a product to beinjected, like blood (as in transfusion of blood from a donor to arecipient or reintroduction of blood from a patient back to the patient)or insulin.

VII.C. A coated vessel or container as described herein and/or preparedaccording to a method described herein can further be used forprotecting a compound or composition contained in its interior spaceagainst mechanical and/or chemical effects of the surface of theuncoated vessel material. For example, it can be used for preventing orreducing precipitation and/or clotting or platelet activation of thecompound or a component of the composition, for example insulinprecipitation or blood clotting or platelet activation.

VII.C. It can further be used for protecting a compound or compositioncontained in its interior against the environment outside of the vessel,for example by preventing or reducing the entry of one or more compoundsfrom the environment surrounding the vessel into the interior space ofthe vessel. Such environmental compound can be a gas or liquid, forexample an atmospheric gas or liquid containing oxygen, air, and/orwater vapor.

VII.C. A coated vessel as described herein can also be evacuated andstored in an evacuated state. For example, the coating allows bettermaintenance of the vacuum in comparison to a corresponding uncoatedvessel. In one aspect of this embodiment, the coated vessel is a bloodcollection tube. The tube can also contain an agent for preventing bloodclotting or platelet activation, for example EDTA or heparin.

VII.C. Any of the above-described embodiments can be made, for example,by providing as the vessel a length of tubing from about 1 cm to about200 cm, optionally from about 1 cm to about 150 cm, optionally fromabout 1 cm to about 120 cm, optionally from about 1 cm to about 100 cm,optionally from about 1 cm to about 80 cm, optionally from about 1 cm toabout 60 cm, optionally from about 1 cm to about 40 cm, optionally fromabout 1 cm to about 30 cm long, and processing it with a probe electrodeas described below. Particularly for the longer lengths in the aboveranges, it is contemplated that relative motion between the probe andthe vessel can be useful during coating formation. This can be done, forexample, by moving the vessel with respect to the probe or moving theprobe with respect to the vessel.

VII.C. In these embodiments, it is contemplated that the coating can bethinner or less complete than can be preferred for a barrier coating, asthe vessel in some embodiments will not require the high barrierintegrity of an evacuated blood collection tube.

VII.C. As an optional feature of any of the foregoing embodiments thevessel has a central axis.

VII.C. As an optional feature of any of the foregoing embodiments thevessel wall is sufficiently flexible to be flexed at least once at 20°C., without breaking the wall, over a range from at least substantiallystraight to a bending radius at the central axis of not more than 100times as great as the outer diameter of the vessel.

VII.C. As an optional feature of any of the foregoing embodiments thebending radius at the central axis is not more than 90 times as greatas, or not more than 80 times as great as, or not more than 70 times asgreat as, or not more than 60 times as great as, or not more than 50times as great as, or not more than 40 times as great as, or not morethan 30 times as great as, or not more than 20 times as great as, or notmore than 10 times as great as, or not more than 9 times as great as, ornot more than 8 times as great as, or not more than 7 times as great as,or not more than 6 times as great as, or not more than 5 times as greatas, or not more than 4 times as great as, or not more than 3 times asgreat as, or not more than 2 times as great as, or not more than, theouter diameter of the vessel.

VII.C. As an optional feature of any of the foregoing embodiments thevessel wall can be a fluid-contacting surface made of flexible material.

VII.C. As an optional feature of any of the foregoing embodiments thevessel lumen can be the fluid flow passage of a pump.

VII.C. As an optional feature of any of the foregoing embodiments thevessel can be a blood bag adapted to maintain blood in good conditionfor medical use.

VII.C., VII.D. As an optional feature of any of the foregoingembodiments the polymeric material can be a silicone elastomer or athermoplastic polyurethane, as two examples, or any material suitablefor contact with blood, or with insulin.

VII.C., VII.D. In an optional embodiment, the vessel has an innerdiameter of at least 2 mm, or at least 4 mm.

VII.C. As an optional feature of any of the foregoing embodiments thevessel is a tube.

VII.C. As an optional feature of any of the foregoing embodiments thelumen has at least two open ends.

VII.C.1. Vessel Containing Viable Blood, Having a Coating Deposited froman Organosilicon Precursor

VII.C.1. Even another embodiment is a blood containing vessel. Severalnon-limiting examples of such a vessel are a blood transfusion bag, ablood sample collection vessel in which a sample has been collected, thetubing of a heart-lung machine, a flexible-walled blood collection bag,or tubing used to collect a patient's blood during surgery andreintroduce the blood into the patient's vasculature. If the vesselincludes a pump for pumping blood, a particularly suitable pump is acentrifugal pump or a peristaltic pump. The vessel has a wall; the wallhas an inner surface defining a lumen. The inner surface of the wall hasan at least partial coating of a hydrophobic layer, characterized asdefined in the Definition Section. The coating can be as thin asmonomolecular thickness or as thick as about 1000 nm. The vesselcontains blood viable for return to the vascular system of a patientdisposed within the lumen in contact with the hydrophobic layer.

VII.C.1. An embodiment is a blood containing vessel including a wall andhaving an inner surface defining a lumen. The inner surface has an atleast partial coating of a hydrophobic layer. The coating can alsocomprise or consist essentially of SiO_(x), where x is as defined inthis specification. The thickness of the coating is within the rangefrom monomolecular thickness to about 1000 nm thick on the innersurface. The vessel contains blood viable for return to the vascularsystem of a patient disposed within the lumen in contact with thehydrophobic layer or coating .

VII.C.2. Coating Deposited from an Organosilicon Precursor ReducesClotting or Platelet Activation of Blood in the Vessel

VII.C.2. Another embodiment is a vessel having a wall. The wall has aninner surface defining a lumen and has an at least partial coating of ahydrophobic layer, where optionally w, x, y, and z are as previouslydefined in the Definition Section. The thickness of the coating is frommonomolecular thickness to about 1000 nm thick on the inner surface. Thecoating is effective to reduce the clotting or platelet activation ofblood exposed to the inner surface, compared to the same type of walluncoated with a hydrophobic layer.

VII.C.2. It is contemplated that the incorporation of a hydrophobiclayer or coating will reduce the adhesion or clot forming tendency ofthe blood, as compared to its properties in contact with an unmodifiedpolymeric or SiO_(x) surface. This property is contemplated to reduce orpotentially eliminate the need for treating the blood with heparin, asby reducing the necessary blood concentration of heparin in a patientundergoing surgery of a type requiring blood to be removed from thepatient and then returned to the patient, as when using a heart-lungmachine during cardiac surgery. It is contemplated that this will reducethe complications of surgery involving the passage of blood through sucha vessel, by reducing the bleeding complications resulting from the useof heparin.

VII.C.2. Another embodiment is a vessel including a wall and having aninner surface defining a lumen. The inner surface has an at leastpartial coating of a hydrophobic layer, the thickness of the coatingbeing from monomolecular thickness to about 1000 nm thick on the innersurface, the coating being effective to reduce the clotting or plateletactivation of blood exposed to the inner surface.

VII.C.3. Vessel Containing Viable Blood, Having a Coating of Group IIIor IV Element

VII.C.3. Another embodiment is a blood containing vessel having a wallhaving an inner surface defining a lumen. The inner surface has an atleast partial coating of a composition comprising one or more elementsof Group III, one or more elements of Group IV , or a combination of twoor more of these. The thickness of the coating is between monomolecularthickness and about 1000 nm thick, inclusive, on the inner surface. Thevessel contains blood viable for return to the vascular system of apatient disposed within the lumen in contact with the hydrophobic layer.

VII.C.4. Coating of Group III or IV Element Reduces Clotting or PlateletActivation of Blood in the Vessel

VII.C.4. Optionally, in the vessel of the preceding paragraph, thecoating of the Group III or IV Element is effective to reduce theclotting or platelet activation of blood exposed to the inner surface ofthe vessel wall.

VII.D. Pharmaceutical Delivery Vessels

VII.D. A coated vessel or container as described herein can be used forpreventing or reducing the escape of a compound or composition containedin the vessel into the environment surrounding the vessel.

Further uses of the coating and vessel as described herein, which areapparent from any part of the description and claims, are alsocontemplated.

VII.D.1. Vessel Containing Insulin, Having a Coating Deposited from anOrganosilicon Precursor

VII.D.1. Another embodiment is an insulin containing vessel including awall having an inner surface defining a lumen. The inner surface has anat least partial coating of a hydrophobic layer, characterized asdefined in the Definition Section. The coating can be from monomolecularthickness to about 1000 nm thick on the inner surface. Insulin isdisposed within the lumen in contact with the Si_(w)O_(x)C_(y)H_(z)coating.

VII.D.1. Still another embodiment is an insulin containing vesselincluding a wall and having an inner surface defining a lumen. The innersurface has an at least partial coating of a hydrophobic layer,characterized as defined in the Definition Section, the thickness of thecoating being from monomolecular thickness to about 1000 nm thick on theinner surface. Insulin, for example pharmaceutical insulin FDA approvedfor human use, is disposed within the lumen in contact with thehydrophobic layer.

VII.D.1. It is contemplated that the incorporation of a hydrophobiclayer, characterized as defined in the Definition Section, will reducethe adhesion or precipitation forming tendency of the insulin in adelivery tube of an insulin pump, as compared to its properties incontact with an unmodified polymeric surface. This property iscontemplated to reduce or potentially eliminate the need for filteringthe insulin passing through the delivery tube to remove a solidprecipitate.

VII.D.2. Coating Deposited from an Organosilicon Precursor ReducesPrecipitation of Insulin in the Vessel

VII.D.2. Optionally, in the vessel of the preceding paragraph, thecoating of a hydrophobic layer or coating is effective to reduce theformation of a precipitate from insulin contacting the inner surface,compared to the same surface absent the hydrophobic layer.

VII.D.2. Even another embodiment is a vessel again comprising a wall andhaving an inner surface defining a lumen. The inner surface includes anat least partial coating of a hydrophobic layer. The thickness of thecoating is in the range from monomolecular thickness to about 1000 nmthick on the inner surface. The coating is effective to reduce theformation of a precipitate from insulin contacting the inner surface.

VII.D.3. Vessel Containing Insulin, Having a Coating of Group III or IVElement

VII.D.3. Another embodiment is an insulin containing vessel including awall having an inner surface defining a lumen. The inner surface has anat least partial coating of a composition comprising carbon, one or moreelements of Group III, one or more elements of Group IV, or acombination of two or more of these. The coating can be frommonomolecular thickness to about 1000 nm thick on the inner surface.Insulin is disposed within the lumen in contact with the coating.

VII.D.4. Coating of Group III or IV Element Reduces Precipitation ofInsulin in the Vessel

VII.D.4. Optionally, in the vessel of the preceding paragraph, thecoating of a composition comprising carbon, one or more elements ofGroup III, one or more elements of Group IV, or a combination of two ormore of these, is effective to reduce the formation of a precipitatefrom insulin contacting the inner surface, compared to the same surfaceabsent the coating.

Common Conditions for All Embodiments

In any embodiment contemplated here, many common conditions can be used,for example any of the following, in any combination. Alternatively, anydifferent conditions described elsewhere in this specification or claimscan be employed.

I. Substrate of Any Embodiment

I.A. Vessel of any embodiment

The vessel can be a sample collection tube, for example a bloodcollection tube, or a syringe, or a syringe part, for example a barrelor piston or plunger; a vial; a conduit; or a cuvette. The substrate canbe a closed-ended tube, for example a medical sample collection tube.The substrate can be the inside wall of a vessel having a lumen, thelumen having a void volume of from 0.5 to 50 mL, optionally from 1 to 10mL, optionally from 0.5 to 5 mL, optionally from 1 to 3 mL. Thesubstrate surface can be part or all of the inner surface of a vesselhaving at least one opening and an inner surface, and wherein thegaseous reactant fills the interior lumen of the vessel and the plasmacan be generated in part or all of the interior lumen of the vessel.

I.B. Syringe and parts

The substrate can be a syringe barrel. The syringe barrel can have aplunger sliding surface and the coating can be disposed on at least aportion of the plunger sliding surface. The coating can be a lubricitylayer. The lubricity layer or coating can be on the barrel interiorsurface. The lubricity layer or coating can be on the plunger. In aparticular aspect, the substrate is a staked needle syringe or part of astaked needle syringe.

I.C. Vessel to receive Stopper

The substrate can be a stopper receiving surface in the mouth of avessel. The substrate can be a generally conical or cylindrical innersurface of an opening of a vessel adapted to receive a stopper.

I.D. Stopper

The substrate can be a sliding surface of a stopper. The substrates canbe coated by providing a multiplicity of the stoppers located in asingle substantially evacuated vessel. The chemical vapor deposition canbe plasma-enhanced chemical vapor deposition and the stopper can becontacted with the plasma. The chemical vapor deposition can beplasma-enhanced chemical vapor deposition. The plasma can be formedupstream of the stopper, producing plasma product, and the plasmaproduct can be contacted with the stopper.

A closure can define a substrate coated with a coating, optionally astopper coated with a lubricity layer. The substrate can be a closureseated in a vessel defining a lumen and a surface of the closure facingthe lumen can be coated with the coating.

The coating can be effective to reduce the transmission of a metal ionconstituent of the stopper into the lumen of the vessel.

I.E. The Substrate of Any Embodiment

The substrate can be a vessel wall. A portion of the vessel wall incontact with a wall-contacting surface of a closure can be coated withthe coating. The coating can be a composite of material having first andsecond layers. The first layer or coating can interface with theelastomeric stopper. The first layer of the coating can be effective toreduce the transmission of one or more constituents of the stopper intothe vessel lumen. The second layer or coating can interface with theinner wall of the vessel. The second layer can be effective to reducefriction between the stopper and the inner wall of the vessel when thestopper can be seated on the vessel.

Alternatively, the first and second layers of any embodiment can bedefined by a coating of graduated properties containing carbon andhydrogen, in which the proportions of carbon and hydrogen are greater inthe first layer or coating than in the second layer.

The coating of any embodiment can be applied by plasma enhanced chemicalvapor deposition.

The substrate of any embodiment can comprise glass, alternatively apolymer, alternatively a polycarbonate polymer, alternatively an olefinpolymer, alternatively a cyclic olefin copolymer, alternatively apolypropylene polymer, alternatively a polyester polymer, alternativelya polyethylene terephthalate polymer, alternatively a polyethylenenaphthalate polymer, alternatively a combination, composite or blend ofany two or more of the above materials.

II. Gaseous Reactant or Process Gas Limitations of Any Embodiment II.ADeposition Conditions of Any Embodiment

The plasma for PECVD, if used, can be generated at reduced pressure andthe reduced pressure can be less than 300 mTorr, optionally less than200 mTorr, even optionally less than 100 mTorr. The physical andchemical properties of the coating can be set by setting the ratio of O₂to the organosilicon precursor in the gaseous reactant, and/or bysetting the electric power used for generating the plasma.

II.B. Relative Proportions of Gases of Any Embodiment

The process gas can contain this ratio of gases for preparing alubricity coating:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 1 to 100 standard volumes of a carrier gas,    -   from 0.1 to 2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes, of the precursor;    -   from 1 to 100 standard volumes of a carrier gas,    -   from 0.1 to 2 standard volumes    -   of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 3 to 70 standard volumes, of a carrier gas,    -   from 0.1 to 2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes, of the precursor;    -   from 3 to 70 standard volumes of a carrier gas,    -   from 0.1 to 2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 1 to 100 standard volumes of a carrier gas,    -   from 0.2 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes, of the precursor;    -   from 1 to 100 standard volumes of a carrier gas,    -   from 0.2 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 3 to 70 standard volumes of a carrier gas,    -   from 0.2 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes of the precursor;    -   from 3 to 70 standard volumes of a carrier gas,    -   from 0.2 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 1 to 100 standard volumes of a carrier gas,    -   from 0.2 to 1 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes of the precursor;    -   from 1 to 100 standard volumes of a carrier gas,    -   from 0.2 to 1 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 3 to 70 standard volumes of a carrier gas,    -   from 0.2 to 1 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   2 to 4 standard volumes, of the precursor;    -   from 3 to 70 standard volumes of a carrier gas,    -   from 0.2 to 1 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 5 to 100 standard volumes of a carrier gas,    -   from 0.1 to 2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes, of the precursor;    -   from 5 to 100 standard volumes of a carrier gas,    -   from 0.1 to 2 standard volumes    -   of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 10 to 70 standard volumes, of a carrier gas,    -   from 0.1 to 2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes, of the precursor;    -   from 10 to 70 standard volumes of a carrier gas,    -   from 0.1 to 2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 5 to 100 standard volumes of a carrier gas,    -   from 0.5 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes, of the precursor;    -   from 5 to 100 standard volumes of a carrier gas,    -   from 0.5 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 10 to 70 standard volumes, of a carrier gas,    -   from 0.5 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes of the precursor;    -   from 10 to 70 standard volumes of a carrier gas,    -   from 0.5 to 1.5 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   from 5 to 100 standard volumes of a carrier gas,    -   from 0.8 to 1.2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 2 to 4 standard volumes of the precursor;    -   from 5 to 100 standard volumes of a carrier gas,    -   from 0.8 to 1.2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   from 1 to 6 standard volumes of the precursor;    -   From 10 to 70 standard volumes of a carrier gas,    -   from 0.8 to 1.2 standard volumes of an oxidizing agent.

alternatively this ratio:

-   -   2 to 4 standard volumes, of the precursor;    -   from 10 to 70 standard volumes of a carrier gas,    -   from 0.8 to 1.2 standard volumes of an oxidizing agent.

II.C. Precursor of Any Embodiment

The organosilicon precursor has been described elsewhere in thisdescription.

The organosilicon compound can in certain aspects, particularly when alubricity coating is formed, comprise octamethylcyclotetrasiloxane(OMCTS). The organosilicon compound for any embodiment of said certainaspects can consist essentially of octamethycyclotetrasiloxane (OMCTS).The organosilicon compound can in certain aspects, particularly when abarrier coating is formed, be or comprise hexamethyldisiloxane.

The reaction gas can also include a hydrocarbon. The hydrocarbon cancomprise methane, ethane, ethylene, propane, acetylene, or a combinationof two or more of these.

The organosilicon precursor can be delivered at a rate of equal to orless than 6 sccm, optionally equal to or less than 2.5 sccm, optionallyequal to or less than 1.5 sccm, optionally equal to or less than 1.25sccm. Larger vessels or other changes in conditions or scale may requiremore or less of the precursor. The precursor can be provided at lessthan 1 Torr absolute pressure.

II.D. Carrier Gas of Any Embodiment

The carrier gas can comprise or consist of an inert gas, for exampleargon, helium, xenon, neon, another gas that is inert to the otherconstituents of the process gas under the deposition conditions, or anycombination of two or more of these.

II.E. Oxidizing Gas of Any Embodiment

The oxidizing gas can comprise or consist of oxygen (O₂ and/or O₃(commonly known as ozone)), nitrous oxide, or any other gas thatoxidizes the precursor during PECVD at the conditions employed. Theoxidizing gas comprises about 1 standard volume of oxygen. The gaseousreactant or process gas can be at least substantially free of nitrogen.

III. Plasma of Any Embodiment

The plasma of any PECVD embodiment can be formed in the vicinity of thesubstrate. The plasma can in certain cases, especially when preparing anSiOx coating, be a non-hollow-cathode plasma. In other certain cases,especially when preparing a lubricity coating, a non-hollow-cathodeplasma is not desired. The plasma can be formed from the gaseousreactant at reduced pressure. Sufficient plasma generation power inputcan be provided to induce coating formation on the substrate.

IV. RF Power of Any Embodiment

The precursor can be contacted with a plasma made by energizing thevicinity of the precursor with electrodes powered at a frequency of 10kHz to 2.45 GHz, alternatively from about 13 to about 14 MHz.

The precursor can be contacted with a plasma made by energizing thevicinity of the precursor with electrodes powered at radio frequency,optionally at a frequency of from 10 kHz to less than 300 MHz,optionally from 1 to 50 MHz, even optionally from 10 to 15 MHz,optionally at 13.56 MHz.

The precursor can be contacted with a plasma made by energizing thevicinity of the precursor with electrodes supplied with electric powerat from 0.1 to 25 W, optionally from 1 to 22 W, optionally from 1 to 10W, even optionally from 1 to 5 W, optionally from 2 to 4 W, for exampleof 3 W, optionally from 3 to 17 W, even optionally from 5 to 14 W, forexample 6 or 7.5 W, optionally from 7 to 11 W, for example of 8 W.

The precursor can be contacted with a plasma made by energizing thevicinity of the precursor with electrodes supplied with electric powerdensity at less than 10 W/ml of plasma volume, alternatively from 6 W/mlto 0.1 W/ml of plasma volume, alternatively from 5 W/ml to 0.1 W/ml ofplasma volume, alternatively from 4 W/ml to 0.1 W/ml of plasma volume,alternatively from 2 W/ml to 0.2 W/ml of plasma volume.

The plasma can be formed by exciting the reaction mixture withelectromagnetic energy, alternatively microwave energy.

V. Other Process Options of Any Embodiment

The applying step for applying a coating to the substrate can be carriedout by vaporizing the precursor and providing it in the vicinity of thesubstrate.

The chemical vapor deposition employed can be PECVD and the depositiontime can be from 1 to 30 sec, alternatively from 2 to 10 sec,alternatively from 3 to 9 sec. The purposes for optionally limitingdeposition time can be to avoid overheating the substrate, to increasethe rate of production, and to reduce the use of process gas and itsconstituents. The purposes for optionally extending deposition time canbe to provide a thicker coating for particular deposition conditions.

VI. Coating Properties of Any Embodiment VI.A. Lubricity Properties ofAny Embodiment

The vessels (e.g. syringe barrels and/or plungers) coated with alubricity coating according to present invention have a higher lubricity(determined, e.g. by measuring the Fi and/or Fm) than the uncoatedvessels. They also have a higher lubricity than vessels coated with aSiO_(x) coating as described herein. An embodiment can be carried outunder conditions effective to form a lubricated surface of the substratehaving a lower sliding force or breakout force (or optionally both) thanthe untreated substrate. Optionally, the materials and conditions can beeffective to reduce the sliding force or breakout force at least atleast 25 percent, alternatively at least 45 percent, alternatively atleast 60 percent, alternatively more than 60 percent relative to anuncoated syringe barrel. Expressed otherwise, the coating can have alower frictional resistance than the uncoated surface, whereinoptionally the frictional resistance can be reduced by at least 25%,optionally by at least 45%, even optionally by at least 60% incomparison to the uncoated surface.

The break loose force (Fi) and the glide force (Fm) are importantperformance measures for the effectiveness of a lubricity coating. ForFi and Fm, it is desired to have a low, but not too low value. With toolow Fi, which means a too low level of resistance (the extreme beingzero), premature/unintended flow may occur, which might e.g. lead to anunintentional premature or uncontrolled discharge of the content of aprefilled syringe.

In order to achieve a sufficient lubricity (e.g. to ensure that asyringe plunger can be moved in the syringe, but to avoid uncontrolledmovement of the plunger), the following ranges of Fi and Fm should beadvantageously maintained: Fi: 2.5 to 5 lbs, preferably 2.7 to 4.9 lbs,and in particular 2.9 to 4.7 lbs; Fm: 2.5 to 8.0 lbs, preferably 3.3 to7.6 lbs, and in particular 3.3 to 4 lbs.

Further advantageous Fi and Fm values can be found in the Tables of theExamples.

The lubricity coating optionally provides a consistent plunger forcethat reduces the difference between the break loose force (Fi) and theglide force (Fm).

VI.B. Hydrophobicity Properties of Any Embodiment

An embodiment can be carried out under conditions effective to form ahydrophobic layer or coating on the substrate. Optionally, thehydrophobic characteristics of the coating can be set by setting theratio of the O₂ to the organosilicon precursor in the gaseous reactant,and/or by setting the electric power used for generating the plasma.Optionally, the coating can have a lower wetting tension than theuncoated surface, optionally a wetting tension of from 20 to 72 dyne/cm,optionally from 30 to 60 dynes/cm, optionally from 30 to 40 dynes/cm,optionally 34 dyne/cm. Optionally, the coating can be more hydrophobicthan the uncoated surface.

VI.C. Thickness of Any Embodiment

Optionally, the coating can have a thickness determined by transmissionelectron microscopy (TEM), of any amount stated in this disclosure.

For the lubricity coatings described herein, the indicated thicknessranges are representing average thickness, as a certain roughness mayenhance the lubricious properties of the lubricity coating. Thus thethickness of the lubricity coating is advantageously not uniformthroughout the coating (see above). However, a uniformly thick lubricitycoating is also considered. The absolute thickness of the lubricitycoating at single measurement points can be higher or lower than therange limits of the average thickness, with maximum deviations ofpreferably +/−50%, more preferably +/−25% and even more preferably+/−15% from the average thickness. However, it typically varies withinthe thickness ranges given for the average thickness in thisdescription.

VI.D. Composition of Any Embodiment

Optionally, the lubricity coating can be composed ofSi_(w)O_(x)C_(y)H_(z) or SiwNxCyHz. It generally has an atomic ratioSi_(w)O_(x)C_(y) wherein w is 1, x is from about 0.5 to about 2.4, y isfrom about 0.6 to about 3, preferably w is 1, x is from about 0.5 to1.5, and y is from 0.9 to 2.0, more preferably w is 1, x is from 0.7 to1.2 and y is from 0.9 to 2.0. The atomic ratio can be determined by XPS(X-ray photoelectron spectroscopy). Taking into account the H atoms, thecoating may thus in one aspect have the formula Si_(w)O_(x)C_(y)H_(z),for example where w is 1, x is from about 0.5 to about 2.4, y is fromabout 0.6 to about 3, and z is from about 2 to about 9. Typically, theatomic ratios are Si 100: O 80-110: C 100-150 in a particular coating ofpresent invention. Specifically, the atomic ratio may be Si 100: O92-107: C 116-133, and such coating would hence contain 36% to 41%carbon normalized to 100% carbon plus oxygen plus silicon.

Alternatively, w can be 1, x can be from about 0.5 to 1.5 y can be fromabout 2 to about 3, and z can be from 6 to about 9. Alternatively, thecoating can have atomic concentrations normalized to 100% carbon,oxygen, and silicon, as determined by X-ray photoelectron spectroscopy(XPS) of less than 50% carbon and more than 25% silicon. Alternatively,the atomic concentrations are from 25 to 45% carbon, 25 to 65% silicon,and 10 to 35% oxygen. Alternatively, the atomic concentrations are from30 to 40% carbon, 32 to 52% silicon, and 20 to 27% oxygen.Alternatively, the atomic concentrations are from 33 to 37% carbon, 37to 47% silicon, and 22 to 26% oxygen.

Optionally, the atomic concentration of carbon, normalized to 100% ofcarbon, oxygen, and silicon, as determined by X-ray photoelectronspectroscopy (XPS), can be greater than the atomic concentration ofcarbon in the atomic formula for the organosilicon precursor. Forexample, embodiments are contemplated in which the atomic concentrationof carbon increases by from 1 to 80 atomic percent, alternatively from10 to 70 atomic percent, alternatively from 20 to 60 atomic percent,alternatively from 30 to 50 atomic percent, alternatively from 35 to 45atomic percent, alternatively from 37 to 41 atomic percent.

Optionally, the atomic ratio of carbon to oxygen in the coating can beincreased in comparison to the organosilicon precursor, and/or theatomic ratio of oxygen to silicon can be decreased in comparison to theorganosilicon precursor.

Optionally, the coating can have an atomic concentration of silicon,normalized to 100% of carbon, oxygen, and silicon, as determined byX-ray photoelectron spectroscopy (XPS), less than the atomicconcentration of silicon in the atomic formula for the feed gas. Forexample, embodiments are contemplated in which the atomic concentrationof silicon decreases by from 1 to 80 atomic percent, alternatively byfrom 10 to 70 atomic percent, alternatively by from 20 to 60 atomicpercent, alternatively by from 30 to 55 atomic percent, alternatively byfrom 40 to 50 atomic percent, alternatively by from 42 to 46 atomicpercent.

As another option, a coating is contemplated that can be characterizedby a sum formula wherein the atomic ratio C:O can be increased and/orthe atomic ratio Si:O can be decreased in comparison to the sum formulaof the organosilicon precursor.

VI.E. Outgassing Species of Any Embodiment

The lubricity coating can have as an outgas component one or moreoligomers containing repeating —(Me)₂SiO— moieties, as determined by gaschromatography/mass spectrometry. The coating outgas component can bedetermined by gas chromatography/mass spectrometry. For example, thecoating outgas component can have at least 10 ng/test of oligomerscontaining repeating —(Me)₂SiO— moieties, alternatively at least 20ng/test of oligomers containing repeating —(Me)₂SiO— moieties, asdetermined using the following test conditions:

-   -   GC Column: 30m×0.25 mm DB-5MS (J&W Scientific), 0.25 μm film        thickness    -   Flow rate 1.0 ml/min, constant flow mode    -   Detector: Mass Selective Detector (MSD)    -   Injection Mode: Split injection (10:1 split ratio)    -   Outgassing Conditions: 1½″ (37 mm) Chamber, purge for three hour        at 85° C., flow 60 ml/min    -   Oven temperature: 40° C. (5 min.) to 300° C. @10° C./min.; hold        for 5 min. at 300° C.

Optionally, the lubricity coating can have an outgas component at leastsubstantially free of trimethylsilanol.

VI.E. Other Coating Properties of Any Embodiment

The coating can have a density between 1.25 and 1.65 g/cm³,alternatively between 1.35 and 1.55 g/cm³, alternatively between 1.4 and1.5 g/cm³, alternatively between 1.4 and 1.5 g/cm³, alternativelybetween 1.44 and 1.48 g/cm³, as determined by X-ray reflectivity (XRR).Optionally, the organosilicon compound can beoctamethylcyclotetrasiloxane and the coating can have a density whichcan be higher than the density of a coating made from HMDSO as theorganosilicon compound under the same PECVD reaction conditions.

The coating optionally can prevent or reduce the precipitation of acompound or component of a composition in contact with the coating, inparticular can prevent or reduce insulin precipitation or bloodclotting, in comparison to the uncoated surface and/or to a barriercoated surface using HMDSO as precursor.

The substrate can be a vessel, for protecting a compound or compositioncontained or received in the coated vessel against mechanical and/orchemical effects of the surface of the uncoated substrate.

The substrate can be a vessel, for preventing or reducing precipitationand/or clotting of a compound or a component of the composition incontact with the interior surface of the vessel. The compound orcomposition can be a biologically active compound or composition, forexample a medicament, for example the compound or composition cancomprise insulin, wherein insulin precipitation can be reduced orprevented. Alternatively, the compound or composition can be abiological fluid, for example a bodily fluid, for example blood or ablood fraction wherein blood clotting can be reduced or prevented.

VII. Plus SIO_(x) Coating, Optional for Any Embodiment

The coating on a substrate, for example a vessel wall, as well ascomprising a lubricity coating, additionally can comprise at least onelayer or coating of SiOx, wherein x can be from 1.5 to 2.9, adjacent tothe coating on the substrate, alternatively between the coating and thesubstrate, alternatively on the opposite side of the coating as thesubstrate. Optionally, the layers of SiOx and the coating can eitherform a sharp interface or a graded composite of Si_(w)O_(x)C_(y)H_(z) toSiO_(x) or vice versa. The substrate coated with a lubricity coating canfurther comprise a surface treatment of the coating in an amounteffective to reduce the leaching of the coating, the substrate, or both.For example, the coating and surface treatment can be composed andpresent in relative amounts effective to provide a breakout force,sliding force, or both less than the corresponding force required in theabsence of the coating and surface treatment. Optionally, the surfacetreatment can be less than 100 nm deep, alternatively less than 50 nmdeep, alternatively less than 40 nm deep, alternatively less than 30 nmdeep, alternatively less than 20 nm deep, alternatively less than 10 nmdeep, alternatively less than 5 nm deep, alternatively less than 3 nmdeep, alternatively less than 1 nm deep, alternatively less than 0.5 nmdeep in the lubricity layer. As another contemplated option, the surfacetreatment can be between 0.1 and 50 nm deep in the lubricity layer.

The optional surface treatment can comprise SiO_(x), in which x can befrom about 1.5 to about 2.9. Optionally, at least a second layer orcoating of SiOx, wherein x can be from 1.5 to 2.9, can be appliedbetween the coating and the substrate surface.

Embodiments are contemplated in which the substrate is a vessel havingan interior surface defining a lumen and an exterior surface. Thelubricity coating can be on the interior surface of the vessel, and thevessel can contain at least one further layer or coating on its exteriorsurface of SiO_(x), wherein x can be from 1.5 to 2.9. Alternatively, thefurther layer or coating on the exterior surface can comprisepolyvinylidene chloride (PVDC). The further layer or coating on theexterior surface optionally can be a barrier coating.

VIII. Product Made of Vessel Plus Contents, Optional for Any Embodiment

In any embodiment, the substrate can be a vessel having an interiorsurface defining a lumen and an exterior surface, the coating can be onthe interior surface of the vessel, and the vessel can contain acompound or composition in its lumen, e.g. citrate or a citratecontaining composition, or e.g. insulin or an insulin containingcomposition. A prefilled syringe is especially considered which containsinjectable or other liquid drugs like insulin.

EXAMPLES

The following Examples are in part already disclosed in EP 2 251 455. Inorder to avoid unnecessary repetition, not all of the Examples in EP 2251 455 A2 are repeated here, but explicit reference is herewith made tothem.

Basic Protocols for Forming and Coating Syringe Barrels

The vessels tested in the subsequent working examples were formed andcoated according to the following exemplary protocols, except asotherwise indicated in individual examples. Particular parameter valuesgiven in the following basic protocols, e.g. the electric power andgaseous reactant or process gas flow, are typical values. Wheneverparameter values were changed in comparison to these typical values,this will be indicated in the subsequent working examples. The sameapplies to the type and composition of the gaseous reactant or processgas.

Protocol for Coating Tube Interior with SiO_(x)

The apparatus as shown in FIG. 1 with the sealing mechanism of FIG. 10,which is a specific contemplated embodiment, was used. The vessel holder50 was made from Delrin® acetal resin, available from E.I. du Pont deNemours and Co., Wilmington Delaware, USA, with an outside diameter of1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vesselholder 50 was housed in a Delrin® structure that allowed the device tomove in and out of the electrode (160).

The electrode 160 was made from copper with a Delrin® shield. TheDelrin® shield was conformal around the outside of the copper electrode160. The electrode 160 measured approximately 3 inches (76 mm) high(inside) and was approximately 0.75 inches (19 mm) wide.

The tube used as the vessel 80 was inserted into the vessel holder 50base sealing with Viton® O-rings 490, 504 (Viton® is a trademark ofDuPont Performance Elastomers LLC, Wilmington Delaware, USA) around theexterior of the tube (FIG. 10). The tube 80 was carefully moved into thesealing position over the extended (stationary) ⅛-inch (3-mm) diameterbrass probe or counter electrode 108 and pushed against a copper plasmascreen.

The copper plasma screen 610 was a perforated copper foil material (K&SEngineering, Chicago Illinois, USA, Part #LXMUWS copper mesh) cut to fitthe outside diameter of the tube, and was held in place by a radiallyextending abutment surface 494 that acted as a stop for the tubeinsertion (see FIG. 10). Two pieces of the copper mesh were fit snuglyaround the brass probe or counter electrode 108, insuring goodelectrical contact.

The brass probe or counter electrode 108 extended approximately 70 mminto the interior of the tube and had an array of #80 wire(diameter=0.0135 inch or 0.343 mm). The brass probe or counter electrode108 extended through a Swagelok® fitting (available from Swagelok Co.,Solon Ohio, USA) located at the bottom of the vessel holder 50,extending through the vessel holder 50 base structure. The brass probeor counter electrode 108 was grounded to the casing of the RF matchingnetwork.

The gas delivery port 110 was 12 holes in the probe or counter electrode108 along the length of the tube (three on each of four sides oriented90 degrees from each other) and two holes in the aluminum cap thatplugged the end of the gas delivery port 110. The gas delivery port 110was connected to a stainless steel assembly comprised of Swagelok®fittings incorporating a manual ball valve for venting, a thermocouplepressure gauge and a bypass valve connected to the vacuum pumping line.In addition, the gas system was connected to the gas delivery port 110allowing the gaseous reactant or process gases, oxygen andhexamethyldisiloxane (HMDSO) to be flowed through the gas delivery port110 (under process pressures) into the interior of the tube.

The gas system was comprised of a Aalborg® GFC17 mass flow meter (Part #EW-32661-34, Cole-Parmer Instrument Co., Barrington Ill. USA) forcontrollably flowing oxygen at 90 sccm (or at the specific flow reportedfor a particular example) into the process and a polyether ether ketone(“PEEK”) capillary (outside diameter, “OD” 1/16-inch (1.5-mm.), insidediameter, “ID” 0.004 inch (0.1 mm)) of length 49.5 inches (1.26 m). ThePEEK capillary end was inserted into liquid hexamethyldisiloxane(“HMDSO,” Alfa Aesar® Part Number L16970, NMR Grade, available fromJohnson Matthey PLC, London). The liquid HMDSO was pulled through thecapillary due to the lower pressure in the tube during processing. TheHMDSO was then vaporized into a vapor at the exit of the capillary as itentered the low pressure region.

To ensure no condensation of the liquid HMDSO past this point, the gasstream (including the oxygen) was diverted to the pumping line when itwas not flowing into the interior of the tube for processing via aSwagelok® 3-way valve. Once the tube was installed, the vacuum pumpvalve was opened to the vessel holder 50 and the interior of the tube.

An Alcatel rotary vane vacuum pump and blower comprised the vacuum pumpsystem. The pumping system allowed the interior of the tube to bereduced to pressure(s) of less than 200 mTorr while the gaseous reactantor process gases were flowing at the indicated rates.

Once the base vacuum level was achieved, the vessel holder 50 assemblywas moved into the electrode 160 assembly. The gas stream (oxygen andHMDSO vapor) was flowed into the brass gas delivery port 110 (byadjusting the 3-way valve from the pumping line to the gas delivery port110). Pressure inside the tube was approximately 300 mTorr as measuredby a capacitance manometer (MKS) installed on the pumping line near thevalve that controlled the vacuum. In addition to the tube pressure, thepressure inside the gas delivery port 110 and gas system was alsomeasured with the thermocouple vacuum gauge that was connected to thegas system. This pressure was typically less than 8 Torr.

Once the gas was flowing to the interior of the tube, the RF powersupply was turned on to its fixed power level. A ENI ACG-6 600 Watt RFpower supply was used (at 13.56 MHz) at a fixed power level ofapproximately 50 Watts. The output power was calibrated in this and allfollowing Protocols and Examples using a Bird Corporation Model 43 RFWatt meter connected to the RF output of the power supply duringoperation of the coating apparatus. The following relationship was foundbetween the dial setting on the power supply and the output power: RFPower Out=55×Dial Setting. In the priority applications to the presentapplication, a factor 100 was used, which was incorrect. The RF powersupply was connected to a COMDEL CPMX1000 auto match which matched thecomplex impedance of the plasma (to be created in the tube) to the 50ohm output impedance of the ENI ACG-6 RF power supply. The forward powerwas 50 Watts (or the specific amount reported for a particular example)and the reflected power was 0 Watts so that the applied power wasdelivered to the interior of the tube. The RF power supply wascontrolled by a laboratory timer and the power on time set to 5 seconds(or the specific time period reported for a particular example). Uponinitiation of the RF power, a uniform plasma was established inside theinterior of the tube. The plasma was maintained for the entire 5 secondsuntil the RF power was terminated by the timer. The plasma produced asilicon oxide coating of approximately 20 nm thickness (or the specificthickness reported in a particular example) on the interior of the tubesurface.

After coating, the gas flow was diverted back to the vacuum line and thevacuum valve was closed. The vent valve was then opened, returning theinterior of the tube to atmospheric pressure (approximately 760 Torr).The tube was then carefully removed from the vessel holder 50 assembly(after moving the vessel holder 50 assembly out of the electrode 160assembly).

Protocol for Forming COC Syringe Barrel

Syringe barrels for an extended barrel syringe (“COC syringe barrels”),CV Holdings Part 11447, can be used, each having a 2.8 mL overall volume(excluding the Luer fitting) and a nominal 1 mL delivery volume orplunger displacement, Luer adapter type, were injection molded fromTopas® 8007-04 cyclic olefin copolymer (COC) resin, available fromHoechst AG, Frankfurt am Main, Germany, having these dimensions: about51 mm overall length, 8.6 mm inner syringe barrel diameter and 1.27 mmwall thickness at the cylindrical portion, with an integral 9.5millimeter length needle capillary Luer adapter molded on one end andtwo finger flanges molded near the other end.

Protocol for Coating COC Syringe Barrel Interior with SiO_(x)

An injection molded COC syringe barrel can be interior coated withSiO_(x). The apparatus as shown in FIG. 1 was modified to hold a COCsyringe barrel with butt sealing at the base of the COC syringe barrel.Additionally a cap was fabricated out of a stainless steel Luer fittingand a polypropylene cap that sealed the end of the COC syringe barrel(illustrated in FIG. 8), allowing the interior of the COC syringe barrelto be evacuated.

The vessel holder 50 can be made from Delrin® with an outside diameterof 1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vesselholder 50 can be housed in a Delrin® structure that allowed the deviceto move in and out of the electrode 160.

The electrode 160 can be made from copper with a Delrin® shield. TheDelrin® shield can be conformal around the outside of the copperelectrode 160. The electrode 160 can be approximately 3 inches (76 mm)high (inside) and approximately 0.75 inches (19 mm) wide. The COCsyringe barrel can be inserted into the vessel holder 50, base sealingwith an Viton® O-rings.

The COC syringe barrel can be carefully moved into the sealing positionover the extended (stationary) ⅛-inch (3-mm.) diameter brass probe orcounter electrode 108 and pushed against a copper plasma screen. Thecopper plasma screen can be a perforated copper foil material (K&SEngineering Part #LXMUW5 Copper mesh) cut to fit the outside diameter ofthe COC syringe barrel and can be held in place by a abutment surface494 that acted as a stop for the COC syringe barrel insertion. Twopieces of the copper mesh were fit snugly around the brass probe orcounter electrode 108 insuring good electrical contact.

The probe or counter electrode 108 extended approximately 20 mm into theinterior of the COC syringe barrel and can be open at its end. The brassprobe or counter electrode 108 extended through a Swagelok® fittinglocated at the bottom of the vessel holder 50, extending through thevessel holder 50 base structure. The brass probe or counter electrode108 can be grounded to the casing of the RF matching network.

The gas delivery port 110 can be connected to a stainless steel assemblycomprised of Swagelok® fittings incorporating a manual ball valve forventing, a thermocouple pressure gauge and a bypass valve connected tothe vacuum pumping line. In addition, the gas system can be connected tothe gas delivery port 110 allowing the gaseous reactant or processgases, oxygen and hexamethyldisiloxane (HMDSO) to be flowed through thegas delivery port 110 (under process pressures) into the interior of theCOC syringe barrel.

The gas system can be comprised of a Aalborg® GFC17 mass flow meter(Cole Parmer Part # EW-32661-34) for controllably flowing oxygen at 90sccm (or at the specific flow reported for a particular example) intothe process and a PEEK capillary (OD 1/16-inch (3-mm) ID 0.004 inches(0.1 mm)) of length 49.5 inches (1.26 m) or other length as indicated ina particular example. The PEEK capillary end can be inserted into liquidhexamethyldisiloxane (Alfa Aesar® Part Number L16970, NMR Grade). Theliquid HMDSO can be pulled through the capillary due to the lowerpressure in the COC syringe barrel during processing. The HMDSO can bethen vaporized into a vapor at the exit of the capillary as it enteredthe low pressure region.

To ensure no condensation of the liquid HMDSO past this point, the gasstream (including the oxygen) can be diverted to the pumping line whenit was not flowing into the interior of the COC syringe barrel forprocessing via a Swagelok® 3-way valve.

Once the COC syringe barrel was installed, the vacuum pump valve can beopened to the vessel holder 50 and the interior of the COC syringebarrel. An Alcatel rotary vane vacuum pump and blower comprised thevacuum pump system. The pumping system allowed the interior of the COCsyringe barrel to be reduced to pressure(s) of less than 150 mTorr whilethe gaseous reactant or process gases were flowing at the indicatedrates. A lower pumping pressure can be achievable with the COC syringebarrel, as opposed to the tube, because the COC syringe barrel has amuch smaller internal volume.

After the base vacuum level was achieved, the vessel holder 50 assemblywas moved into the electrode 160 assembly. The gas stream (oxygen andHMDSO vapor) was flowed into the brass gas delivery port 110 (byadjusting the 3-way valve from the pumping line to the gas delivery port110). The pressure inside the COC syringe barrel is approximately 200mTorr as measured by a capacitance manometer (MKS) installed on thepumping line near the valve that controlled the vacuum. In addition tothe COC syringe barrel pressure, the pressure inside the gas deliveryport 110 and gas system is also measured with the thermocouple vacuumgauge that is connected to the gas system. This pressure is typicallyless than 8 Torr.

When the gas is flowing to the interior of the COC syringe barrel, theRF power supply is turned on to its fixed power level. A ENI ACG-6 600Watt RF power supply is used (at 13.56 MHz) at a fixed power level ofapproximately 30 Watts. The RF power supply is connected to a COMDELCPMX1000 auto match that matched the complex impedance of the plasma (tobe created in the COC syringe barrel) to the 50 ohm output impedance ofthe ENI ACG-6 RF power supply. The forward power is 30 Watts (orwhatever value is reported in a working example) and the reflected poweris 0 Watts so that the power is delivered to the interior of the COCsyringe barrel. The RF power supply is controlled by a laboratory timerand the power on time set to 5 seconds (or the specific time periodreported for a particular example).

Upon initiation of the RF power, a uniform plasma is established insidethe interior of the COC syringe barrel. The plasma is maintained for theentire 5 seconds (or other coating time indicated in a specific example)until the RF power is terminated by the timer. The plasma produced asilicon oxide coating of approximately 20 nm thickness (or the thicknessreported in a specific example) on the interior of the COC syringebarrel surface.

After coating, the gas flow is diverted back to the vacuum line and thevacuum valve is closed. The vent valve is then opened, returning theinterior of the COC syringe barrel to atmospheric pressure(approximately 760 Torr). The COC syringe barrel is then carefullyremoved from the vessel holder 50 assembly (after moving the vesselholder 50 assembly out of the electrode 160 assembly).

Protocol for Coating COC Syringe Barrel Interior with OMCTS LubricityLayer or Coating

COC syringe barrels as previously identified were interior coated with alubricity layer. The apparatus as shown in FIG. 1 is modified to hold aCOC syringe barrel with butt sealing at the base of the COC syringebarrel. Additionally a cap is fabricated out of a stainless steel Luerfitting and a polypropylene cap that sealed the end of the COC syringebarrel (illustrated in FIG. 8). The installation of a Buna-N O-ring ontothe Luer fitting allowed a vacuum tight seal, allowing the interior ofthe COC syringe barrel to be evacuated.

The vessel holder 50 is made from Delrin® with an outside diameter of1.75 inches (44 mm) and a height of 1.75 inches (44 mm). The vesselholder 50 is housed in a Delrin® structure that allowed the device tomove in and out of the electrode 160.

The electrode 160 is made from copper with a Delrin® shield. The Delrin®shield is conformal around the outside of the copper electrode 160. Theelectrode 160 measured approximately 3 inches (76 mm) high (inside) andis approximately 0.75 inches (19 mm) wide. The COC syringe barrel isinserted into the vessel holder 50, base sealing with Viton® O-ringsaround the bottom of the finger flanges and lip of the COC syringebarrel.

The COC syringe barrel is carefully moved into the sealing position overthe extended (stationary) ⅛-inch (3-mm.) diameter brass probe or counterelectrode 108 and pushed against a copper plasma screen. The copperplasma screen is a perforated copper foil material (K&S Engineering Part#LXMUW5 Copper mesh) cut to fit the outside diameter of the COC syringebarrel and is held in place by a abutment surface 494 that acted as astop for the COC syringe barrel insertion. Two pieces of the copper meshwere fit snugly around the brass probe or counter electrode 108 insuringgood electrical contact.

The probe or counter electrode 108 extended approximately 20 mm (unlessotherwise indicated) into the interior of the COC syringe barrel and isopen at its end. The brass probe or counter electrode 108 extendedthrough a Swagelok® fitting located at the bottom of the vessel holder50, extending through the vessel holder 50 base structure. The brassprobe or counter electrode 108 is grounded to the casing of the RFmatching network.

The gas delivery port 110 is connected to a stainless steel assemblycomprised of Swagelok® fittings incorporating a manual ball valve forventing, a thermocouple pressure gauge and a bypass valve connected tothe vacuum pumping line. In addition, the gas system is connected to thegas delivery port 110 allowing the gaseous reactant or process gas,octamethylcyclotetrasiloxane (OMCTS) (or the specific gaseous reactantor process gas reported for a particular example) to be flowed throughthe gas delivery port 110 (under process pressures) into the interior ofthe COC syringe barrel.

The gas system is comprised of a commercially available HoribaVC1310/SEF8240 OMCTS 10SC 4CR heated mass flow vaporization system thatheated the OMCTS to about 100° C. The Horiba system is connected toliquid octamethylcyclotetrasiloxane (Alfa Aesar® Part Number A12540,98%) through a ⅛-inch (3-mm) outside diameter PFA tube with an insidediameter of 1/16 in (1.5 mm). The OMCTS flow rate is set to 1.25 sccm(or the specific organosilicon precursor flow reported for a particularexample). To ensure no condensation of the vaporized OMCTS flow pastthis point, the gas stream is diverted to the pumping line when it isnot flowing into the interior of the COC syringe barrel for processingvia a Swagelok® 3-way valve.

Once the COC syringe barrel is installed, the vacuum pump valve isopened to the vessel holder 50 and the interior of the COC syringebarrel. An Alcatel rotary vane vacuum pump and blower comprise- thevacuum pump system. The pumping system allows the interior of the COCsyringe barrel to be reduced to pressure(s) of less than 100 mTorr whilethe gaseous reactant or process gases is flowing at the indicated rates.A lower pressure can be obtained in this instance, compared to the tubeand previous COC syringe barrel examples, because the overall gaseousreactant or process gas flow rate is lower in this instance.

Once the base vacuum level is achieved, the vessel holder 50 assembly ismoved into the electrode 160 assembly. The gas stream (OMCTS vapor) isflowed into the brass gas delivery port 110 (by adjusting the 3-wayvalve from the pumping line to the gas delivery port 110). Pressureinside the COC syringe barrel is approximately 140 mTorr as measured bya capacitance manometer (MKS) installed on the pumping line near thevalve that controlled the vacuum. In addition to the COC syringe barrelpressure, the pressure inside the gas delivery port 110 and gas systemis also measured with the thermocouple vacuum gauge that is connected tothe gas system. This pressure is typically less than 6 Torr.

Once the gas is flowing to the interior of the COC syringe barrel, theRF power supply is turned on to its fixed power level. A ENI ACG-6 600Watt RF power supply is used (at 13.56 MHz) at a fixed power level ofapproximately 6 Watts (or other power level indicated in a specificexample). The RF power supply is connected to a COMDEL CPMX1000 automatch which matched the complex impedance of the plasma (to be createdin the COC syringe barrel) to the 50 ohm output impedance of the ENIACG-6 RF power supply. The forward power is 6 Watts and the reflectedpower is 0 Watts so that 6 Watts of power (or a different power leveldelivered in a given example) is delivered to the interior of the COCsyringe barrel. The RF power supply is controlled by a laboratory timerand the power on time set to 10 seconds (or a different time stated in agiven example).

Upon initiation of the RF power, a uniform plasma is established insidethe interior of the COC syringe barrel. The plasma is maintained for theentire coating time, until the RF power is terminated by the timer. Theplasma produced a lubricity layer or coating on the interior of the COCsyringe barrel surface.

After coating, the gas flow is diverted back to the vacuum line and thevacuum valve is closed. The vent valve is then opened, returning theinterior of the COC syringe barrel to atmospheric pressure(approximately 760 Torr). The COC syringe barrel is then carefullyremoved from the vessel holder 50 assembly (after moving the vesselholder 50 assembly out of the electrode 160 assembly).

Protocol for Coating COC Syringe Barrel Interior with HMDSO Coating

The Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer or coating is also used for applying an HMDSO coating,except substituting HMDSO for OMCTS.

Protocol for Lubricity Testing

VII.B.1.a. The following materials is used in this test:

-   -   Commercial (BD Hypak® PRTC) glass prefillable syringes with        Luer-lok® tip) (ca 1 mL)    -   COC syringe barrels made according to the Protocol for Forming        COC Syringe barrel;    -   Commercial plastic syringe plungers with elastomeric tips taken        from Becton Dickinson Product No. 306507 (obtained as saline        prefilled syringes);    -   Normal saline solution (taken from the Becton-Dickinson Product        No. 306507 prefilled syringes);    -   Dillon Test Stand with an Advanced Force Gauge (Model AFG-50N)    -   Syringe holder and drain jig (fabricated to fit the Dillon Test        Stand)

VII.B.1.a. The following procedure is used in this test.

VII.B.1.a. The jig is installed on the Dillon Test Stand. The platformprobe movement is adjusted to 6 in/min (2.5 mm/sec) and upper and lowerstop locations were set. The stop locations were verified using an emptysyringe and barrel. The commercial saline-filled syringes were labeled,the plungers were removed, and the saline solution is drained via theopen ends of the syringe barrels for re-use. Extra plungers wereobtained in the same manner for use with the COC and glass barrels.

VII.B.1.a. Syringe plungers were inserted into the COC syringe barrelsso that the second horizontal molding point of each plunger is even withthe syringe barrel lip (about 10 mm from the tip end). Using anothersyringe and needle assembly, the test syringes were filled via thecapillary end with 2-3 milliliters of saline solution, with thecapillary end uppermost. The sides of the syringe were tapped to removeany large air bubbles at the plunger/ fluid interface and along thewalls, and any air bubbles were carefully pushed out of the syringewhile maintaining the plunger in its vertical orientation.

VII.B.1.a. Each filled syringe barrel/plunger assembly is installed intothe syringe jig. The test is initiated by pressing the down switch onthe test stand to advance the moving metal hammer toward the plunger.When the moving metal hammer is within 5 mm of contacting the top of theplunger, the data button on the Dillon module is repeatedly tapped torecord the force at the time of each data button depression, from beforeinitial contact with the syringe plunger until the plunger is stopped bycontact with the front wall of the syringe barrel.

VII.B.1.a. All benchmark and coated syringe barrels were run with fivereplicates (using a new plunger and barrel for each replicate).

VII.B.1.a. COC syringe barrels made according to the Protocol forForming COC Syringe barrel were coated with an OMCTS lubricity layer orcoating according to the Protocol for Coating COC Syringe BarrelInterior with OMCTS Lubricity layer, except at a power of 7.5 Watts,assembled and filled with saline, and tested as described above in thisExample for lubricity layers. The polypropylene chamber used per theProtocol for Coating COC Syringe Barrel Interior with OMCTS Lubricitylayer or coating allowed the OMCTS vapor (and oxygen, if added) to flowthrough the syringe barrel and through the syringe capillary into thepolypropylene chamber (although a lubricity layer or coating can not beneeded in the capillary section of the syringe in this instance).Different coating conditions were tested. All of the depositions werecompleted on COC syringe barrels from the same production batch.

VII.B.1.a. The samples were created by coating COC syringe barrelsaccording to the Protocol for Coating COC Syringe Barrel Interior withOMCTS Lubricity layer. An alternative embodiment of the technologyherein, would apply the lubricity layer or coating over another thinfilm coating, such as SiO_(x), for example applied according to theProtocol for Coating COC Syringe barrel Interior with SiO_(x).

Instead of the Dillon Test Stand and drain jig, a Genesis PackagingPlunger Force Tester (Model SFT-01 Syringe Force Tester, manufactured byGenesis Machinery, Lionville, Pa.) can also be used following themanufacturer's instructions for measuring Fi and Fm. The parameters thatare used on the Genesis tester are:

Start: 10 mm

Speed: 100 mm/min

Range: 20

Units: Newtons

Working Examples in addition to the Working Examples presented in EP 2251 455 A2 which are also understood as Working Examples for the presentinvention.

Examples A-D

Syringe samples were produced as follows. A COC 8007 extended barrelsyringe was produced according to the Protocol for Forming COC SyringeBarrel. An SiOx coating was applied to some of the syringes according tothe Protocol for Coating COC Syringe Barrel Interior with SiOx. Alubricity coating was applied to the SiOx coated syringes according tothe Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer, modified as follows. The OMCTS was supplied from avaporizer, due to its low volatility. Argon carrier gas was used. Theprocess conditions were set to the following:

-   -   OMCTS—3 sccm    -   Argon gas—65 sccm    -   Power—6 watts    -   Time—10 seconds

The coater was later determined to have a small leak while producing theL2 samples identified in the Table, which resulted in an estimatedoxygen flow of 1.0 sccm. The L3 samples were produced withoutintroducing oxygen.

Several syringes were then tested for lubricity using a GenesisPackaging Plunger Force Tester (Model SFT-01 Syringe Force Tester,manufactured by Genesis Machinery, Lionville, Pa.) according to theProtocol for Lubricity Testing. Both the initiation force andmaintenance forces (in Newtons) were noted relative to an uncoatedsample, and are reported in Table 1.

Syringes coated with silicon oil were included as a reference since thisis the current industry standard.

Examples E-H

Syringe samples were produced as follows. A COC 8007 extended barrelsyringe was produced according to the Protocol for Forming COC SyringeBarrel. An SiOx coating was applied to the syringe barrels according tothe Protocol for Coating COC Syringe Barrel Interior with SiOx. Alubricity coating was applied to the SiOx coated syringes according tothe Protocol for Coating COC Syringe Barrel Interior with OMCTSLubricity layer, modified as follows. The OMCTS was supplied from avaporizer, due to its low volatility. Argon carrier gas and oxygen wereused where noted in Table 2. The process conditions were set to thefollowing, or as indicated in Table 2:

-   -   OMCTS—3 sccm (when used)    -   Argon gas—7.8 sccm (when used)    -   Oxygen 0.38 sccm (when used)    -   Power—3 watts    -   Power on time—10 seconds

Syringes E and F prepared under these conditions, Syringes G preparedunder these conditions except without a lubricity coating, and SyringesH (a commercial syringe coated with silicon oil) were then tested forlubricity using a Genesis Packaging Plunger Force Tester according tothe Protocol for Lubricity Testing. Both the initiation force andmaintenance forces (in Newtons) were noted relative to an uncoatedsample, and are reported in Table 2. Syringes coated with silicon oilwere included as a reference since this is the current industrystandard.

The lubricity results are shown in Table 2 (Initiation Force andMaintenance Force), illustrating under these test conditions as wellthat the lubricity coating on Syringes E and F markedly improved theirlubricity compared to Syringes G which lacked any lubricity coating. Thelubricity coating on Syringes E and F also markedly improved theirlubricity compared to Syringes H which contained the standard lubricitycoating in the industry.

Syringes E, F, and G were also tested to determine total extractablesilicon levels (representing extraction of the organosilicon-based PECVDcoatings) using an Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)analysis.

The silicon was extracted using saline water digestion. The tip of eachsyringe plunger was covered with PTFE tape to prevent extractingmaterial from the elastomeric tip material, then inserted into thesyringe barrel base. The syringe barrel was filled with two millilitersof 0.9% aqueous saline solution via a hypodermic needle inserted throughthe Luer tip of the syringe. This is an appropriate test forextractables because many prefilled syringes are used to contain anddeliver saline solution. The Luer tip was plugged with a piece of PTFEbeading of appropriate diameter. The syringe was set into a PTFE teststand with the Luer tip facing up and placed in an oven at 50° C. for 72hours.

Then, either a static or a dynamic mode was used to remove the salinesolution from the syringe barrel. According to the static mode indicatedin Table 2, the syringe plunger was removed from the test stand, and thefluid in the syringe was decanted into a vessel. According to thedynamic mode indicated in Table 2, the Luer tip seal was removed and theplunger was depressed to push fluid through the syringe barrel and expelthe contents into a vessel. In either case, the fluid obtained from eachsyringe barrel was brought to a volume of 50 ml using 18.2 MΩ*cmdeionized water and further diluted 2× to minimize sodium backgroundduring analysis. The CVH barrels contained two milliliters and thecommercial barrels contained 2.32 milliliters.

Next, the fluid recovered from each syringe was tested for extractablesilicon using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)Analysis. The instrument: used was a Perkin Elmer Elan DRC II equippedwith a Cetac ASX-520 autosampler. The following ICP-MS conditions wereemployed:

-   -   Nebulizer: Quartz Meinhardt    -   Spray Chamber: Cyclonic    -   RF (radio frequency) power: 1550 Watts    -   Argon (Ar) Flow: 15.0 L/min    -   Auxiliary Ar Flow: 1.2 L/min    -   Nebulizer Gas Flow: 0.88 L/min    -   Integration time: 80 sec    -   Scanning mode: Peak hopping    -   RPq (The RPq is a rejection parameter) for Cerium as CeO (m/z        156): <2%

Aliquots from aqueous dilutions obtained from Syringes E, F, and G wereinjected and analyzed for Si in concentration units of micrograms perliter. The results of this test are shown in Table 2. While the resultsare not quantitative, they do indicate that extractables from thelubricity coating are not clearly higher than the extractables for theSiOx barrier layer only. Also, the static mode produced far lessextractables than the dynamic mode, which was expected.

Examples I-K

Syringe samples I, J, and K, employing three different lubricitycoatings, were produced in the same manner as for Examples E-H except asfollows or as indicated in Table 3:

-   -   OMCTS−2.5 sccm    -   Argon gas−7.6 sccm (when used)    -   Oxygen 0.38 sccm (when used)    -   Power—3 watts    -   Power on time—10 seconds

Syringe I had a three-component coating employing OMCTS, oxygen, andcarrier gas. Syringe J had a two component coating employing OMCTS andoxygen, but no carrier gas. Syringe K had a one-component coating (OMCTSonly). Syringes I, J, and K were then tested for lubricity as describedfor Examples E-H.

The lubricity results are shown in Table 3 (Initiation Force andMaintenance Force). Syringe I with a three-component coating employingOMCTS, oxygen, and carrier gas provided the best lubricity results forboth initiation force and maintenance force. Syringe J omitting thecarrier gas yielded intermediate results. Syringe K had a one-componentcoating (OMCTS only), and provided the lowest lubricity. This exampleshows that the addition of both a carrier gas and oxygen to the processgas improved lubricity under the tested conditions.

Examples L-N

Examples I-K using an OMCTS precursor gas were repeated in Examples L-N,except that HMDSO was used as the precursor in Examples L-N. The resultsare shown in Table 3. The results show that for the testedthree-component, two-component, and one-component lubricity coatings,the OMCTS coatings provided lower resistance, thus better lubricity,than the HMDSO coatings, demonstrating the value of OMCTS as theprecursor gas for lubricity coatings.

Examples O-V, W, X, Y

In these examples the surface roughness of the lubricity coatings wascorrelated with lubricity performance.

OMCTS coatings were applied with previously described equipment with theindicated specific process conditions (Table 5) onto one milliliter COC6013 molded syringe barrels. Plunger force measurements (Fi, Fm) (Table5) were performed with previously described equipment under the sameprotocols. Scanning electron spectroscopy (SEM) photomicrographs (Table5, FIGS. 16 to 20) and atomic force microscopy (AFM) Root Mean Square(RMS) and other roughness determinations (Tables 5 and 6) were madeusing the procedures indicated below. Average RMS values are taken fromthree different RMS readings on the surface. The plunger force tests,AFM and SEM tests reported in table 5 were performed on differentsamples due to the nature of the individual tests which prohibited aperformance of all tests on one sample.

Comparison of Fi/Fm to SEM photomicrograph to AFM Average RMS valuesclearly indicates that lower plunger forces are realized withnon-continuous, rougher OMCTS plasma-coated surfaces (cf. Samples O to Qvs. R to V; FIG. 18-20).

Further testing was carried out on sister samples Examples W, X, and Y,respectively made under conditions similar to Example Q, T, and V, toshow the Fi and Fm values corresponding to the AFM roughness data.Example W which has a higher surface roughness (compare Example Q inFIG. 18, Table 5) has much lower Fi and Fm friction values (Table 6)than Example X (compare Example T in FIG. 19) or Y. The Fm test shown inTable 6 was interrupted before reaching the measured value of Fm forExamples X and Y because the Fm value was too high.

SEM Procedure

SEM Sample Preparation: Each syringe sample was cut in half along itslength (to expose the interior surface). The top of the syringe (Luerend) was cut off to make the sample smaller.

The sample was mounted onto the sample holder with conductive graphiteadhesive, then put into a Denton Desk IV SEM Sample Preparation System,and a thin (approximately 50 Å) thick gold coating was sputtered ontothe interior surface of the syringe. The gold coating is required toeliminate charging of the surface during measurement.

The sample was removed from the sputter system and mounted onto thesample stage of a Jeol JSM 6390 SEM (Scanning Electron Microscope). Thesample was pumped down to at least 1×10⁻⁶ Torr in the samplecompartment. Once the sample reached the required vacuum level, the slitvalve was opened and the sample was moved into the analysis station.

The sample was imaged at a coarse resolution first, then highermagnification images were accumulated. The SEM images provided in theFigures are 5 μm edge-to-edge (horizontal and vertical).

AFM (Atomic Force Microscopy) Procedure.

AFM images were collected using a NanoScope III Dimension 3000 machine(Digital Instruments, Santa Barbara, California, USA). The instrumentwas calibrated against a NIST traceable standard. Etched siliconscanning probe microscopy (SPM) tips were used. Image processingprocedures involving auto-flattening, plane fitting or convolution wereemployed. One 10 μm×10 μm area was imaged. Roughness analyses wereperformed and were expressed in: (1) Root-Mean-Square Roughness, RMS;(2) Mean Roughness, Ra; and (3) Maximum Height (Peak-to-Valley), Rmax,all measured in nm (see Table 5 and FIGS. 18 to 20). For the roughnessanalyses, each sample was imaged over the 10 μm×10 μm area, followed bythree cross sections selected by the analyst to cut through features inthe 10 μm×10 μm images. The vertical depth of the features was measuresusing the cross section tool. For each cross section, a Root-Mean-SquareRoughness (RMS) in nanmeters was reported. These RMS values along withthe average of the three cross sections for each sample are listed inTable 5.

Additional analysis of the 10 μm×10 μm images represented by FIGS. 18 to20 (Examples Q, T and V) was carried out. For this analysis three crosssections were extracted from each image. The locations of the crosssections were selected by the analyst to cut through features in theimages. The vertical depth of the features was measured using the crosssection tool.

The Digital Instruments Nanoscope III AFM/STM acquires and stores3-dimensional representations of surfaces in a digital format. Thesesurfaces can be analyzed in a variety of ways.

The Nanoscope III software can perform a roughness analysis of any AFMor STM image. The product of this analysis is a single color pagereproducing the selected image in top view. To the upper right of theimage is the “Image Statistics” box, which lists the calculatedcharacteristics of the whole image minus any areas excluded by astopband (a box with an X through it). Similar additional statistics canbe calculated for a selected portion of the image and these are listedin the “Box Statistics” in the lower right portion of the page. Whatfollows is a description and explanation of these statistics.

Image Statistics:

Z Range (R_(p)): The difference between the highest and lowest points inthe image. The value is not corrected for tilt in the plane of theimage; therefore, plane fitting or flattening the data will change thevalue.

Mean: The average of all of the Z values in the imaged area. This valueis not corrected for the tilt in the plane of the image; therefore,plane fitting or flattening the data will change this value.

RMS (R_(q)): This is the standard deviation of the Z values (or RMSroughness) in the image. It is calculated according to the formula:

R_(q)={Σ(Z₁-Z_(avg))2/N}

where Zavg is the average Z value within the image; Z1 is the currentvalue of Z; and N is the number of points in the image. This value isnot corrected for tilt in the plane of the image; therefore, planefitting or flattening the data will change this value.

Mean roughness (R_(a)): This is the mean value of the surface relativeto the Center Plane and is calculated using the formula:

R _(a)=[1/(L _(x) L _(y))]ƒ_(o) ^(Ly)ƒ_(o) ^(Lx) {f(x,y)}dxdy

where f(x,y) is the surface relative to the Center plane, and L_(x) andL_(y) are the dimensions of the surface.

Max height (R_(max)): This is the difference in height between thehighest and lowest points of the surface relative to the Mean Plane.

Surface area: (Optical calculation): This is the area of the3-dimensional surface of the imaged area. It is calculated by taking thesum of the areas of the triangles formed by 3 adjacent data pointsthroughout the image.

Surface area diff: (Optional calculation) This is the amount that theSurface area is in excess of the imaged area. It is expressed as apercentage and is calculated according to the formula:

Surface area diff=100[(Surface area/S ₁2)−1]

where S₁ is the length (and width) of the scanned area minus any areasexcluded by stopbands.

Center Plane: A flat plane that is parallel to the Mean Plane. Thevolumes enclosed by the image surface above and below the center planeare equal.

Mean Plane: The image data has a minimum variance about this flat plane.It results from a first order least squares fit on the Z data.

Summary of Lubricity Measurements

Table 8 shows a summary of the above OMCTS coatings and their Fi and Fmvalues. It has to be understood that the initial lubricity coating work(C-K; roughness not known) was to identify the lowest possible plungerforce attainable. From subsequent market input, it was determined thatthe lowest achievable plunger force was not necessarily most desirable,for reasons explained in the generic description (e.g. prematurerelease). Thus, the PECVD reaction parameters were varied to obtain aplunger force of practical market use.

Example Z: Lubricity Coating Extractables

Total silicon extractables were measured using ICP-MS analysis. Thesyringes were evaluated in both static and dynamic situations. Thefollowing describes the test procedure:

Syringe filled with 2 ml of 0.9% saline solution

Syringe placed in a stand—stored at 50° C. for 72 hours.

After 72 hours saline solution test for total silicon

Total silicon measure before and after saline solution expelled throughsyringe.

The extractable Silicon Levels from a silicon oil coated glass syringeand a Lubricity coated and SiO₂ coated COC syringe are shown in Table 7.Precision of the ICP-MS total silicon measurement is +/−3%.

TABLE 1 PLUNGER SLIDING FORCE MEASUREMENTS OF OMCTS-BASED PLASMACOATINGS MADE WITH CARRIER GAS Carrier Lubricity Gas Lubricity LubricityOMCTS Lubricity (Ar) Layer or Coating Flow O2 Flow Flow CoatingInitiation Maintenance Coating coating Time Rate Rate Rate Power Force,F_(i) Force, F_(m) Example Type Monomer (sec) (sccm) (sccm) (sccm)(Watts) (N, Kg.) (N, Kg.) A Uncoated n/a n/a n/a n/a n/a n/a >11N >11N(Control) COC >1.1 Kg. >1.1 Kg. B Silicon oil n/a n/a n/a n/a n/a n/a 8.2N  6.3N (Industry on COC 0.84 Kg. 0.64 Kg. Standard) C L3 OMCTS 10sec 3 0 65 6 4.6N 4.6N (without Lubricity 0.47 Kg. 0.47 Kg. Oxygen)layer or coating over SiO_(x) on COC D L2 OMCTS 10 sec 3 1 65 6 4.8N3.5N (with Lubricity 0.49 Kg. 0.36 Kg. Oxygen) layer or coating overSiO_(x) on COC

TABLE 2 OMCTS Lubricity Coatings (E and F) Ini- Mainte- tiation nanceICPMS Exam- OMCTS O₂ Ar Force, Force, (μg./ ICPMS ple (sccm) (sccm)(sccm) Fi (N) Fm (N) liter) Mode E 3.0 0.38 7.8 4.8 3.5 <5 static F 3.00.38 7.8 5.4 4.3 38 dynamic G n/a n/a n/a 13 11 <5 static (SiOx only) Hn/a n/a n/a 8.2 6.3 (silicon oil)

TABLE 3 OMCTS Lubricity Coatings Initiation Maintenance OMCTS O₂ ArForce, Force, Example (sccm) (sccm) (sccm) Fi (N) Fm (N) I 2.5 0.38 7.65.1 4.4 J 2.5 0.38 — 7.1 6.2 K 2.5 — — 8.2 7.2

TABLE 4 HMDSO Coatings Initiation Maintenance HMDSO O₂ Ar Force, Force,Example (sccm) (sccm) (sccm) Fi (N) Fm (N) L 2.5 0.38 7.6 9 8.4 M 2.50.38 — >11 >11 N 2.5 — — >11 >11

TABLE 5 SEM Dep. Micrograph OMCTS Ar/O₂ Power Time Plunger Force (5micronAF AFM RMS Example (sccm) (sccm) (Watts) (sec) Fi (lbs, Kg) Fm(lbs, Kg) Vertical) (nanometers) O Baseline 2.0 10/0.38 3.5 10 4.66,2.11 3.47, 1.57 OMCTS (ave) (ave) P Lubricity FIG. 16 Q 19.6, 9.9, 9.4(Average = 13.0) FIGS. 18A, 18B, 18C R High Power 2.0 10/0.38 4.5 104.9, 2.2 7.6, 3.4 S OMCTS FIG. 17 T Lubricity 12.5, 8.4, 6.1 (Average =6.3) FIG. 19A, 20B, 20C U No O₂ OMCTS 2.0 10/0 3.4 10 4.9, 2.2 9.7, 4.4Lubricity (stopped) V 1.9, 2.6, 3.0 (Average = 2.3) FIG. 20A, 20B, 20C

TABLE 6 Dep. Siloxane Power Time F_(i) (lb., F_(m) (lb., SiO_(x)/LubCoater Mode Feed Ar/O₂ (W) (Sec.) Kg.) Kg.) Example W SiO_(x): Auto-TubeAuto HMDSO 0 sccm Ar, 37 7 ~ ~ SiOx/Baseline 52.5 in, 90 sccm O₂ OMCTSLub 133.4 cm. Lubricity: Auto-S same OMCTS, 10 sccm Ar 3.4 10 2.9, 3.3,1.5 2.0 sccm 0.38 sccm O₂ 1.3 Example X SiO_(x): same same same same 377 ~ ~ SiOx/High Lubricity: same same same same 4.5 10 5, 2.3 9.5, 4.3Pwr OMCTS stopped Lub Example Y SiOx: Auto-Tube same same 0 sccm Ar, 377 ~ ~ SiOx/No O₂ 90 sccm O₂ OMCTS Lub Lubricity: Auto-S same same 10sccm Ar 3.4 10 5.6, 9.5, 4.3 0 sccm O₂ stopped

TABLE 7 Silicon Extractables Comparison of Lubricity Coatings PackageType Static (ug/L) Dynamic (ug/L) Cyclic Olefin Syringe with CV 70 81Holdings SiOCH Lubricity Coating Borocilicate Glass Syringe with 825 835silicone oil

TABLE 8 Summary Table of OMCTS coatings from Tables 1, 2, 3 and 5 DepExam- OMCTS O₂ Ar Power Time ple (sccm) (sccm) (sccm) (Watt) (sec)F_(i)(lbs) F_(m)(lbs) C 3.0 0.00 65 6 10 1.0 1.0 D 3.0 1.00 65 6 10 1.10.8 E 3.0 0.38 7.8 6 10 0.8 1.1 F 3.0 0.38 7.8 6 10 1.2 1.0 I 2.5 0.387.6 6 10 1.1 1.0 J 2.5 0.38 0.0 6 10 1.6 1.4 K 2.5 0.00 0.0 6 10 1.8 1.6O 2.0 0.38 10 3.5 10 4.6 3.5 R 2.0 0.38 10 4.5 10 4.9 7.6 U 2.0 0.00 103.4 10 4.9 9.7(stop) W 2.0 0.38 10 3.4 10 2.9 3.3 X 2.0 0.38 10 4.5 105.0 9.5 (stop) Y 2.0 0.00 10 3.4 10 5.6 9.5 (stop)

While the invention has been illustrated and described in detail in thedrawings and foregoing description, such illustration and descriptionare to be considered illustrative or exemplary and not restrictive; theinvention is not limited to the disclosed embodiments. Other variationsto the disclosed embodiments can be understood and effected by thoseskilled in the art and practising the claimed invention, from a study ofthe drawings, the disclosure, and the appended claims. In the claims,the word “comprising” does not exclude other elements or steps, and theindefinite article “a” or “an” does not exclude a plurality. The merefact that certain measures are recited in mutually different dependentclaims does not indicate that a combination of these measures cannot beused to advantage. Any reference signs in the claims should not beconstrued as limiting the scope.

1. (canceled)
 2. A syringe comprising a barrel and a plunger, the barrelhaving an interior surface coated at least in part with a lubricitycoating made by: (a) providing a gas comprising a monocyclic siloxane,O₂, and a noble gas, in the vicinity of the interior surface; and (b)generating a plasma in the gas, thus forming a coating on the interiorsurface by plasma enhanced chemical vapor deposition (PECVD) underconditions effective to form a lubricity coating on the interior surfacecomprising a crosslinked monocyclic siloxane chemical structure andhaving a plunger initiation force F_(i) of 4.8 to 11 N.
 3. The syringeof claim 2, in which the plunger initiation force F_(i) is from 5.1 to11 N.
 4. The syringe of claim 2, in which the plunger initiation forceF_(i) is from 5.4 to 11 N.
 5. The syringe of claim 2, in which theplunger maintenance force F_(m) is from 3.5 to 11 N.
 6. The syringe ofclaim 2, in which the plunger maintenance force F_(m) is from 4.3 to 11N.
 7. The syringe of claim 2, in which the plunger maintenance forceF_(m) is from 4.4 to 11 N.
 8. The syringe according to claim 2 whichcontains a medicament in contact with the lubricity coating.
 9. Thesyringe of claim 2, wherein the lubricity coating has an atomic ratioSi_(w)O_(x)C_(y) or Si_(w)N_(x)C_(y) wherein w is 1, x is from about 0.5to about 2.4, and y is from about 0.6 to about
 3. 10. The syringe ofclaim 2, wherein the lubricity coating has an average thickness of from10 to 1000 nm.
 11. The syringe of claim 2, wherein the syringe barrel isCOC, wherein the gas in step (a) comprises octamethylcyclotetrasiloxane,O₂ and Ar, and wherein the plasma is generated by applying a powerdensity from 6 W/ml to 0.1 W/ml in relation to the volume of the syringelumen.
 12. The syringe of claim 2, which contains a medicament.
 13. Thesyringe of claim 2, in which the monocyclic siloxane comprisesoctamethylcyclotetrasiloxane (OMCTS).
 14. The syringe of claim 2, inwhich the plunger initiation force F_(i) is from 4.8 to 11 N and theplunger maintenance force F_(m) is from 3.5 to 11 N.